Editorial

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Special Issue “Role of Redox Homeostasis and Oxidative Stress in Human Health”

by Hung-Yao Ho

Int. J. Mol. Sci. 2023, 24(9), 8352; https://doi.org/10.3390/ijms24098352 - 06 May 2023

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Abstract

Redox homeostasis plays essential roles in the regulation of the physiological process [...] Full article

(This article belongs to the Special Issue Role of Redox Homeostasis and Oxidative Stress in Human Health)

Research

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18 pages, 3556 KiB

Open AccessArticle

Dual Role of Mitogen-Activated Protein Kinase 8 Interacting Protein-1 in Inflammasome and Pancreatic β-Cell Function

by Rania Saeed, Abdul Khader Mohammed, Sarra E. Saleh, Mohammad M. Aboulwafa, Khaled M. Aboshanab and Jalal Taneera

Int. J. Mol. Sci. 2023, 24(5), 4990; https://doi.org/10.3390/ijms24054990 - 05 Mar 2023

Cited by 2 | Viewed by 1538

Abstract

Inflammasomes have been implicated in the pathogenesis of type 2 diabetes (T2D). However, their expression and functional importance in pancreatic β-cells remain largely unknown. Mitogen-activated protein kinase 8 interacting protein-1 (MAPK8IP1) is a scaffold protein that regulates JNK signaling and is involved in [...] Read more.

Inflammasomes have been implicated in the pathogenesis of type 2 diabetes (T2D). However, their expression and functional importance in pancreatic β-cells remain largely unknown. Mitogen-activated protein kinase 8 interacting protein-1 (MAPK8IP1) is a scaffold protein that regulates JNK signaling and is involved in various cellular processes. The precise role of MAPK8IP1 in inflammasome activation in β-cells has not been defined. To address this gap in knowledge, we performed a set of bioinformatics, molecular, and functional experiments in human islets and INS-1 (832/13) cells. Using RNA-seq expression data, we mapped the expression pattern of proinflammatory and inflammasome-related genes (IRGs) in human pancreatic islets. Expression of MAPK8IP1 in human islets was found to correlate positively with key IRGs, including the NOD-like receptor (NLR) family pyrin domain containing 3 (NLRP3), Gasdermin D (GSDMD) and Apoptosis-associated speck-like protein containing a CARD (ASC), but correlate inversely with Nuclear factor kappa β1 (NF-κβ1), Caspase-1 (CASP-1), Interleukin-18 (IL-18), Interleukin-1β (IL-1β) and Interleukin 6 (IL-6). Ablation of Mapk8ip1 by siRNA in INS-1 cells down-regulated the basal expression levels of Nlrp3, NLR family CARD domain containing 4 (Nlrc4), NLR family CARD domain containing 1 (Nlrp1), Casp1, Gsdmd, Il-1β, Il-18, Il-6, Asc, and Nf-κβ1 at the mRNA and/or protein level and decreased palmitic acid (PA)-induced inflammasome activation. Furthermore, Mapk8ip1-silened cells substantially reduced reactive oxygen species (ROS) generation and apoptosis in palmitic acid-stressed INS-1 cells. Nonetheless, silencing of Mapk8ip1 failed to preserve β-cell function against inflammasome response. Taken together, these findings suggest that MAPK8IP1 is involved in regulating β-cells by multiple pathways. Full article

(This article belongs to the Special Issue Role of Redox Homeostasis and Oxidative Stress in Human Health)

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18 pages, 2038 KiB

Open AccessArticle

Calpain Regulates Reactive Oxygen Species Production during Capacitation through the Activation of NOX2 and NOX4

by César I. Ortiz-García, Monica L. Salgado-Lucio, Ana L. Roa-Espitia, Aidé A. Muñoz-Sánchez, Joaquín Cordero-Martínez and Enrique O. Hernández-González

Int. J. Mol. Sci. 2023, 24(4), 3980; https://doi.org/10.3390/ijms24043980 - 16 Feb 2023

Cited by 2 | Viewed by 1299

Abstract

Capacitation is a series of physiological, biochemical, and metabolic changes experienced by mammalian spermatozoa. These changes enable them to fertilize eggs. The capacitation prepares the spermatozoa to undergo the acrosomal reaction and hyperactivated motility. Several mechanisms that regulate capacitation are known, although they [...] Read more.

Capacitation is a series of physiological, biochemical, and metabolic changes experienced by mammalian spermatozoa. These changes enable them to fertilize eggs. The capacitation prepares the spermatozoa to undergo the acrosomal reaction and hyperactivated motility. Several mechanisms that regulate capacitation are known, although they have not been fully disclosed; among them, reactive oxygen species (ROS) play an essential role in the normal development of capacitation. NADPH oxidases (NOXs) are a family of enzymes responsible for ROS production. Although their presence in mammalian sperm is known, little is known about their participation in sperm physiology. This work aimed to identify the NOXs related to the production of ROS in guinea pig and mouse spermatozoa and define their participation in capacitation, acrosomal reaction, and motility. Additionally, a mechanism for NOXs’ activation during capacitation was established. The results show that guinea pig and mouse spermatozoa express NOX2 and NOX4, which initiate ROS production during capacitation. NOXs inhibition by VAS2870 led to an early increase in the capacitation and intracellular concentration of Ca²⁺ in such a way that the spermatozoa also presented an early acrosome reaction. In addition, the inhibition of NOX2 and NOX4 reduced progressive motility and hyperactive motility. NOX2 and NOX4 were found to interact with each other prior to capacitation. This interaction was interrupted during capacitation and correlated with the increase in ROS. Interestingly, the association between NOX2-NOX4 and their activation depends on calpain activation, since the inhibition of this Ca²⁺-dependent protease prevents NOX2-NOX4 from dissociating and ROS production. The results indicate that NOX2 and NOX4 could be the most important ROS producers during guinea pig and mouse sperm capacitation and that their activation depends on calpain. Full article

(This article belongs to the Special Issue Role of Redox Homeostasis and Oxidative Stress in Human Health)

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14 pages, 2313 KiB

Open AccessArticle

Synthesis and Antimicrobial Activity of the Pathogenic E. coli Strains of p-Quinols: Additive Effects of Copper-Catalyzed Addition of Aryl Boronic Acid to Benzoquinones

by Dominik Koszelewski, Paweł Kowalczyk, Jan Samsonowicz-Górski, Anastasiia Hrunyk, Anna Brodzka, Justyna Łęcka, Karol Kramkowski and Ryszard Ostaszewski

Int. J. Mol. Sci. 2023, 24(2), 1623; https://doi.org/10.3390/ijms24021623 - 13 Jan 2023

Cited by 3 | Viewed by 1476

Abstract

A mild and efficient protocol for the synthesis of p-quinols under aqueous conditions was developed. The pivotal role of additives in the copper-catalyzed addition of aryl boronic and heteroaryl boronic acids to benzoquinones was observed. It was found that polyvinylpyrrolidone (PVP) was [...] Read more.

A mild and efficient protocol for the synthesis of p-quinols under aqueous conditions was developed. The pivotal role of additives in the copper-catalyzed addition of aryl boronic and heteroaryl boronic acids to benzoquinones was observed. It was found that polyvinylpyrrolidone (PVP) was the most efficient additive used for the studied reaction. The noteworthy advantages of this procedure include its broad substrate scope, high yields up to 91%, atom economy, and usage of readily available starting materials. Another benefit of this method is the reusability of the catalytic system up to four times. Further, the obtained p-quinols were characterized on the basis of their antimicrobial activities against E. coli. Antimicrobial activity was further compared with the corresponding 4-benzoquinones and 4-hydroquinones. Among tested compounds, seven derivatives showed an antimicrobial activity profile similar to that observed for commonly used antibiotics such as ciprofloxacin, bleomycin, and cloxacillin. In addition, the obtained p-quinols constitute a suitable platform for further modifications, allowing for a convenient change in their biological activity profile. Full article

(This article belongs to the Special Issue Role of Redox Homeostasis and Oxidative Stress in Human Health)

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15 pages, 1385 KiB

Open AccessArticle

Increased Oxidative Stress Markers in Acute Ischemic Stroke Patients Treated with Thrombolytics

by Hanna Pawluk, Renata Kołodziejska, Grzegorz Grześk, Alina Woźniak, Mariusz Kozakiewicz, Agnieszka Kosinska, Mateusz Pawluk, Elżbieta Grzechowiak, Jakub Wojtasik and Grzegorz Kozera

Int. J. Mol. Sci. 2022, 23(24), 15625; https://doi.org/10.3390/ijms232415625 - 09 Dec 2022

Cited by 13 | Viewed by 1429

Abstract

One of the most common neurological disorders involving oxidative stress is stroke. During a stroke, the balance of redox potential in the cell is disturbed, and, consequently, protein oxidation or other intracellular damage occurs, ultimately leading to apoptosis. The pineal gland hormone, melatonin, [...] Read more.

One of the most common neurological disorders involving oxidative stress is stroke. During a stroke, the balance of redox potential in the cell is disturbed, and, consequently, protein oxidation or other intracellular damage occurs, ultimately leading to apoptosis. The pineal gland hormone, melatonin, is one of the non-enzymatic antioxidants. It not only modulates the perianal rhythm but also has anti-inflammatory properties and protects against stress-induced changes. The focus of this research was to evaluate the concentration of the carbonyl groups and melatonin metabolite in time in patients with acute ischemic stroke that were treated with intravenous thrombolysis. This included a comparison of the functional status of patients assessed according to neurological scales with the control sample comprising healthy people. The studies showed that the serum concentrations of carbonyl groups, which were elevated in patients with ischemic stroke (AIS) in comparison to the control samples, had an impact on the patients’ outcome. A urine concentration of the melatonin metabolite, which was lower in patients than controls, was related to functional status after 24 h from cerebral thrombolysis. It shows that determination of carbonyl groups at different time intervals may be an important potential marker of protein damage in patients with AIS treated with cerebral thrombolysis, and that impaired melatonin metabolism induces a low antioxidant protection. Thus, due to the neuroprotective effects of melatonin, attention should also be paid to the design and conduct of clinical trials and hormone supplementation in AIS patients to understand the interactions between exogenous melatonin and its endogenous rhythm, as well as how these relationships may affect patient outcomes. Full article

(This article belongs to the Special Issue Role of Redox Homeostasis and Oxidative Stress in Human Health)

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Review

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21 pages, 1061 KiB

Open AccessReview

Alterations in Lymphocytic Metabolism—An Emerging Hallmark of MS Pathophysiology?

by Viktoria B. Greeck, Sarah K. Williams, Jürgen Haas, Brigitte Wildemann and Richard Fairless

Int. J. Mol. Sci. 2023, 24(3), 2094; https://doi.org/10.3390/ijms24032094 - 20 Jan 2023

Cited by 1 | Viewed by 1429

Abstract

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) characterised by acute inflammation and subsequent neuro-axonal degeneration resulting in progressive neurological impairment. Aberrant immune system activation in the periphery and subsequent lymphocyte migration to the CNS contribute to [...] Read more.

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) characterised by acute inflammation and subsequent neuro-axonal degeneration resulting in progressive neurological impairment. Aberrant immune system activation in the periphery and subsequent lymphocyte migration to the CNS contribute to the pathophysiology. Recent research has identified metabolic dysfunction as an additional feature of MS. It is already well known that energy deficiency in neurons caused by impaired mitochondrial oxidative phosphorylation results in ionic imbalances that trigger degenerative pathways contributing to white and grey matter atrophy. However, metabolic dysfunction in MS appears to be more widespread than the CNS. This review focuses on recent research assessing the metabolism and mitochondrial function in peripheral immune cells of MS patients and lymphocytes isolated from murine models of MS. Emerging evidence suggests that pharmacological modulation of lymphocytic metabolism may regulate their subtype differentiation and rebalance pro- and anti-inflammatory functions. As such, further understanding of MS immunometabolism may aid the identification of novel treatments to specifically target proinflammatory immune responses. Full article

(This article belongs to the Special Issue Role of Redox Homeostasis and Oxidative Stress in Human Health)

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16 pages, 2567 KiB

Open AccessReview

NOX Dependent ROS Generation and Cell Metabolism

by Tiziana Pecchillo Cimmino, Rosario Ammendola, Fabio Cattaneo and Gabriella Esposito

Int. J. Mol. Sci. 2023, 24(3), 2086; https://doi.org/10.3390/ijms24032086 - 20 Jan 2023

Cited by 27 | Viewed by 2748

Abstract

Reactive oxygen species (ROS) represent a group of high reactive molecules with dualistic natures since they can induce cytotoxicity or regulate cellular physiology. Among the ROS, the superoxide anion radical (O2·−) is a key redox signaling molecule prominently generated by the NADPH oxidase [...] Read more.

Reactive oxygen species (ROS) represent a group of high reactive molecules with dualistic natures since they can induce cytotoxicity or regulate cellular physiology. Among the ROS, the superoxide anion radical (O2·−) is a key redox signaling molecule prominently generated by the NADPH oxidase (NOX) enzyme family and by the mitochondrial electron transport chain. Notably, altered redox balance and deregulated redox signaling are recognized hallmarks of cancer and are involved in malignant progression and resistance to drugs treatment. Since oxidative stress and metabolism of cancer cells are strictly intertwined, in this review, we focus on the emerging roles of NOX enzymes as important modulators of metabolic reprogramming in cancer. The NOX family includes seven isoforms with different activation mechanisms, widely expressed in several tissues. In particular, we dissect the contribute of NOX1, NOX2, and NOX4 enzymes in the modulation of cellular metabolism and highlight their potential role as a new therapeutic target for tumor metabolism rewiring. Full article

(This article belongs to the Special Issue Role of Redox Homeostasis and Oxidative Stress in Human Health)

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21 pages, 1462 KiB

Open AccessReview

The Road to Malignant Cell Transformation after Particulate Matter Exposure: From Oxidative Stress to Genotoxicity

by Miguel Santibáñez-Andrade, Ericka Marel Quezada-Maldonado, Andrea Rivera-Pineda, Yolanda I. Chirino, Claudia M. García-Cuellar and Yesennia Sánchez-Pérez

Int. J. Mol. Sci. 2023, 24(2), 1782; https://doi.org/10.3390/ijms24021782 - 16 Jan 2023

Cited by 7 | Viewed by 2623

Abstract

In cells, oxidative stress is an imbalance between the production/accumulation of oxidants and the ability of the antioxidant system to detoxify these reactive products. Reactive oxygen species (ROS), cause multiple cellular damages through their interaction with biomolecules such as lipids, proteins, and DNA. [...] Read more.

In cells, oxidative stress is an imbalance between the production/accumulation of oxidants and the ability of the antioxidant system to detoxify these reactive products. Reactive oxygen species (ROS), cause multiple cellular damages through their interaction with biomolecules such as lipids, proteins, and DNA. Genotoxic damage caused by oxidative stress has become relevant since it can lead to mutation and play a central role in malignant transformation. The evidence describes chronic oxidative stress as an important factor implicated in all stages of the multistep carcinogenic process: initiation, promotion, and progression. In recent years, ambient air pollution by particulate matter (PM) has been cataloged as a cancer risk factor, increasing the incidence of different types of tumors. Epidemiological and toxicological evidence shows how PM-induced oxidative stress could mediate multiple events oriented to carcinogenesis, such as proliferative signaling, evasion of growth suppressors, resistance to cell death, induction of angiogenesis, and activation of invasion/metastasis pathways. In this review, we summarize the findings regarding the involvement of oxidative and genotoxic mechanisms generated by PM in malignant cell transformation. We also discuss the importance of new approaches oriented to studying the development of tumors associated with PM with more accuracy, pursuing the goal of weighing the impact of oxidative stress and genotoxicity as one of the main mechanisms associated with its carcinogenic potential. Full article

(This article belongs to the Special Issue Role of Redox Homeostasis and Oxidative Stress in Human Health)

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21 pages, 790 KiB

Open AccessReview

Salivary Redox Homeostasis in Human Health and Disease

by Beáta Čižmárová, Vladimíra Tomečková, Beáta Hubková, Anna Hurajtová, Jana Ohlasová and Anna Birková

Int. J. Mol. Sci. 2022, 23(17), 10076; https://doi.org/10.3390/ijms231710076 - 03 Sep 2022

Cited by 5 | Viewed by 2413

Abstract

Homeostasis is a self-regulatory dynamic process that maintains a stable internal environment in the human body. These regulations are essential for the optimal functioning of enzymes necessary for human health. Homeostasis elucidates disrupted mechanisms leading to the development of various pathological conditions caused [...] Read more.

Homeostasis is a self-regulatory dynamic process that maintains a stable internal environment in the human body. These regulations are essential for the optimal functioning of enzymes necessary for human health. Homeostasis elucidates disrupted mechanisms leading to the development of various pathological conditions caused by oxidative stress. In our work, we discuss redox homeostasis and salivary antioxidant activity during healthy periods and in periods of disease: dental carries, oral cavity cancer, periodontal diseases, cardiovascular diseases, diabetes mellitus, systemic sclerosis, and pancreatitis. The composition of saliva reflects dynamic changes in the organism, which makes it an excellent tool for determining clinically valuable biomarkers. The oral cavity and saliva may form the first line of defense against oxidative stress. Analysis of salivary antioxidants may be helpful as a diagnostic, prognostic, and therapeutic marker of not only oral, but also systemic health. Full article

(This article belongs to the Special Issue Role of Redox Homeostasis and Oxidative Stress in Human Health)

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