Oxidative Stress-induced Diseases Research Articles

Wavelength-dependent photoelectrochemical sensor array based on Bi2WO6/TiO2 electrospun nanoheterojunction for multiple antioxidants identification and total antioxidant capacity analysis in natural tea

Evaluating total antioxidant capacity (TAC) have been playing a vital role in health guidelines, the analysis of nutritional composition in foods, and the diagnosis and treatment of oxidative stress-induced disease. However, numerous antioxidants with similar physicochemical properties make them very difficult to be discriminated because of the similarly analytical signal output. In this work, a novel wavelength-dependent and three-channel photoelectrochemical (PEC) sensor array based on Bi2WO6/Vo-TiO2 electrospun nanostructures was established for the identification of antioxidants in natural teas. The formation of heterojunction interfaces between Bi2WO6 nanosheet and Vo-TiO2 NFs, and the introduction of the oxygen vacancies in TiO2 NFs promoted the visible light absorption ability and electron transfer rate of Bi2WO6/Vo-TiO2 NFs, causing the differences of photocurrent response to different antioxidants under different wavelengths. Furthermore, excited wavelengths, antioxidant types, and photocurrent were regarded as three-factors of fingerprint to accurately discriminate five antioxidants via linear discriminant analysis (LDA). Finally, the PEC sensor array was able to estimate TAC in five actual tea samples (green, yellow, black, white, and dark teas). This development of LDA-assisted multiplex PEC fingerprinting sensor array showed a good promise for the identification and authentication of agricultural products, and the establishment of the database.

Oxidative Stress-Induced Gastrointestinal Diseases: Biology and Nanomedicines—A Review

Oxidative Stress-Induced Gastrointestinal Diseases: Biology and Nanomedicines—A Review

Carbon dots encapsulated zeolitic imidazolate framework-8 as an enhanced multi-antioxidant for efficient cytoprotection to HK-2 cells

Excessive reactive oxygen species (ROS) can lead to the imbalance of antioxidant system in the body and cause oxidative damage to cells. It is imperative to rationally design nanomaterials with high catalytic activity and multiple antioxidant activities. Here, line peppers-derived carbon dots (CDs) is encapsulated into zeolitic imidazolate framework-8 (CDs@ZIF-8) to achieve enhanced antioxidant activities for improved protective effect on cells. This nanosystem has a broad spectrum of antioxidant properties, which can effectively remove a variety of intracellular ROS and protect cells from ROS-induced death and cytoskeleton damage. In addition, CDs@ZIF-8 can reduce malondialdehyde (MDA) level and increase the enzyme activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx), as well as the level of glutathione (GSH) in human kidney proximal tubular epithelial cells (HK-2) cells. Mechanism studies demonstrated that CDs@ZIF-8 can up-regulate the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1), allowing the regulation of antioxidant enzymes to further achieve antioxidant effect. Besides, CDs@ZIF-8 inhibited the secretion of proinflammatory cytokines. This work demonstrates that the constructed CDs@ZIF-8 with multi-antioxidant activity can act as a highly efficient intracellular ROS scavenger and provide potential for the application in related oxidative stress-induced diseases.

Neuroretinal Cell Culture Model as a Tool for the Development of New Therapeutic Approaches for Oxidative Stress-Induced Ocular Diseases, with a Focus on Glaucoma.

Glaucoma is a heterogeneous group of optic neuropathies characterized by a progressive degeneration of the retinal ganglion cells (RGCs), leading to irreversible vision loss. Nowadays, the traditional therapeutic approach to glaucoma consists of lowering the intraocular pressure (IOP), which does not address the neurodegenerative features of the disease. Besides animal models of glaucoma, there is a considerable need for in vitro experimental models to propose new therapeutic strategies for this ocular disease. In this study, we elucidated the pathological mechanisms leading to neuroretinal R28 cell death after exposure to glutamate and hydrogen peroxide (H2O2) in order to develop new therapeutic approaches for oxidative stress-induced retinal diseases, including glaucoma. We were able to show that glutamate and H2O2 can induce a decrease in R28 cell viability in a concentration-dependent manner. A cell viability of about 42% was found after exposure to 3 mM of glutamate and about 56% after exposure to 100 µM of H2O2 (n = 4). Label-free quantitative mass spectrometry analysis revealed differential alterations of 193 and 311 proteins in R28 cells exposed to 3 mM of glutamate and 100 µM of H2O2, respectively (FDR < 1%; p < 0.05). Bioinformatics analysis indicated that the protein changes were associated with the dysregulation of signaling pathways, which was similar to those observed in glaucoma. Thus, the proteomic alteration induced by glutamate was associated with the inhibition of the PI3K/AKT signaling pathway. On the other hand, H2O2-induced toxicity in R28 cells was linked to the activation of apoptosis signaling and the inhibition of the mTOR and ERK/MAPK signaling pathways. Furthermore, the data show a similarity in the inhibition of the EIF2 and AMPK signaling pathways and the activation of the sumoylation and WNT/β-catenin signaling pathways in both groups. Our findings suggest that the exposure of R28 cells to glutamate and H2O2 could induce glaucoma-like neurodegenerative features and potentially provide a suitable tool for the development of new therapeutic strategies for retinal diseases.

Establishing an Oxidative Stress Model in the Human Mesencephalic Cell Line (LUHMES): an in vitro study

Oxidative stress-caused neurodegenerative diseases, such as Alzheimer's, Parkinson's disease, and amyotrophic lateral sclerosis, are widely recognized as the most prevalent brain and central nervous system disorders. This is attributed to the vulnerability of neurons to oxidative stress within the body. Although substantial research has been performed on these diseases, it is extremely difficult to establish an oxidative stress model for brain tissues. In primary cultures, it is difficult to obtain neurons and the continuity of the culture is limited for in vitro cell line models. By providing valuable insights into the mechanisms of oxidative stress-induced neurodegenerative diseases, these in vitro models can aid in the development of effective treatment strategies. Here, we developed an in vitro oxidative stress model utilizing hydrogen peroxide on the LUHMES cell line. Our study evaluated the impact of this model on LUHMES cell viability and the equilibrium between oxidants and antioxidants by assaying total oxidant capacity (TOC) and total antioxidant capacity (TAC). Our results provided evidence of the oxidative effect of hydrogen peroxide in critical concentration and proved the efficacy of this model for further investigations.

Phytochemical characterization, antioxidant, and antimicrobial activities of the Ayurvedic polyherbal formulation Mentone

Introduction: Polyherbalism is extensively practiced in traditional medicine and constitutes complementary and alternative medicine (CAM). Greater therapeutic efficacy ensues from the synergistic effects of constituents mediated by pharmacodynamic and pharmacokinetic interactions and safety at higher dosages. Very few studies exist on mechanistics, despite rampant polyherbal use. Mentone tablet is a polyherbal constituting equal components of Centella asiatica (L.) Urban, Convolvulus pluricaulis Choisy, Glycyrrhiza glabra L., and Tinospora cordifolia (Willd.) Miers ex Hook. F. and Thomson. Materials and Methods: Proximate and phytochemical analysis followed by quantification of polyphenolics was carried out. Asiatic acid, berberine, betaine, and glycyrrhizin were characterized using ultraviolet–high-performance liquid chromatography (UV-HPLC). Antioxidant activity was determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH) quenching activity, ferric reducing ability of plasma (FRAP) assay, and hydrogen peroxide (H2O2) scavenging activity. Antimicrobial activity was determined by Kirby–Bauer disc diffusion microbial susceptibility test followed by minimum inhibitory concentration (MIC) method. Results: Aqueous extraction using Soxhlet generated maximum yield. Proximate analysis yielded 52.96% ash, pH ranged from 5.75 to 5.76, and 5% moisture content. Qualitative analysis revealed the presence of inorganic substances and phytochemicals: saponins, reducing sugars, terpenoids, starch, glycosides, and triterpenoids. Phenols were higher in aqueous, while flavonoids and tannins were higher in ethanolic extracts. HPLC revealed the presence of glycyrrhizin and asiatic acid. Mentone extracts at 100 µg/mL showed the highest antioxidant activity in DPPH, FRAP assays, and H2O2 radical scavenging. Ethanolic extracts above 50 mg/mL demonstrated antimicrobial activity against Staphylococcus aureus ATCC 25923 and Klebsiella pneumoniae ATCC 700603. Conclusion: Mentone contains phytochemicals with antioxidant and antimicrobial activities. With active constituents such as asiatic acid and glycyrrhizin, Mentone could constitute a CAM for oxidative stress-induced diseases, including neurodegeneration.

A multifactorial study of in situ antioxidant activity of modified GrO in myocardial reperfusion injury using the Langerdorff model

Carbon nanomaterials possess antioxidant properties that can be applied in biomedicine and clinics for the development of new highly effective treatments against oxidative stress-induced diseases like ischemic heart disease. We previously reported the usage of graphene oxide (GrO) as a precursor for the elaboration of such prototypes. The promising findings led to the development of two new modifications of GrO: nitrogen-doped (N-GrO) and l-cysteine functionalized (S-GrO) derivatives as possible antioxidant agents in ischemia-reperfusion (I/R) conditions. In this study, the cardioprotective and antioxidant potential of modified GrO as a pre-treatment in rats was evaluated for the first time. In Langendorff isolated rat heart I/R model, the left ventricle developed pressure (LVDP), the end-diastolic pressure (EDP), the maximal (dP/dtmax) and minimal (dP/dtmin) value of the first derivative of LVDP, and heart rate (HR) were measured. The oxidative-nitrosative markers, in particular, the rate of O2*- and H2O2 generation, the content of malonic dialdehyde, diene conjugates, and leukotriene as well as cNOS and iNOS activity were estimated. Obtained results show a significant restoration of cadiodynamic parameters at the reperfusion period. Simultaneously, all samples significantly reduced the rate of reactive oxygen species (ROS) and lipid peroxidation markers in cardiac homogenates and preserved cNOS activity at the preischemic level. This evidence makes GrO derivatives promising candidates for the correction of reperfusion disorders affecting myocardial function.

Lycopene: A Potent Antioxidant with Multiple Health Benefits.

Lycopene is a naturally occurring carotenoid predominantly found in tomatoes and tomato-based products. Like other phytochemicals, it exhibits health beneficial biological activities that can be exploited when it is used as a dietary supplement. In vitro and in vivo, lycopene has been demonstrated to mitigate oxidative stress-induced metabolic dysfunctions and diseases including inflammation, obesity, and diabetes mellitus. Lycopene has been shown to alleviate metabolic diseases that affect the bone, eye, kidney, liver, lungs, heart, and nervous system. This review presents the state of the art regarding lycopene's health benefits and its potential applications in health system delivery. Furthermore, lycopene's protective effects against toxins, safety in its use, and possible toxicity are explored.

Exploring the multifaceted role of NRF2 in brain physiology and cancer: A comprehensive review.

Chronic oxidative stress plays a critical role in the development of brain malignancies due to the high rate of brain oxygen utilization and concomitant production of reactive oxygen species. The nuclear factor-erythroid-2-related factor 2 (NRF2), a master regulator of antioxidant signaling, is a key factor in regulating brain physiology and the development of age-related neurodegenerative diseases. Also, NRF2 is known to exert a protective antioxidant effect against the onset of oxidative stress-induced diseases, including cancer, along with its pro-oncogenic activities through regulating various signaling pathways and downstream target genes. In glioblastoma (GB), grade 4 glioma, tumor resistance, and recurrence are caused by the glioblastoma stem cell population constituting a small bulk of the tumor core. The persistence and self-renewal capacity of these cell populations is enhanced by NRF2 expression in GB tissues. This review outlines NRF2's dual involvement in cancer and highlights its regulatory role in human brain physiology and diseases, in addition to the development of primary brain tumors and therapeutic potential, with a focus on GB.

Rubi idaei fructus as a Source of Bioactive Chemical Compounds with an Important Role in Human Health and Comparison of the Antioxidant Potential of Fruits and Juice of Three Repeat-Fruiting Rubus idaeus L. Cultivars.

Rubi idaei fructus is a source of nutritionally important bioactive chemical compounds, mainly antioxidants, which strengthen the immune system and can be used in the prophylaxis and adjuvant therapies of many oxidative stress-induced diseases. There are no literature reports presenting a comprehensive comparative analysis of the antioxidant activity and nutritionally relevant metabolites contained in the fruits of repeat-fruiting raspberry cultivars, which are commonly grown in Europe. The aim of this study was to carry out a comparative analysis of the antioxidant potential (Folin-Ciocalteu, DPPH, FRAP), the content of selected primary and secondary metabolites, and the qualitative and quantitative composition of amino acids and fatty acids in the fruits of R. idaeus cv. 'Pokusa', 'Polana', and 'Polka'. The fruits of the analyzed cultivars have a low caloric value (171-219 kcal/100 g); low content of available carbohydrates (6-6.6%) and total carbohydrates (3.4-4.8%); and high levels of dietary fiber (4.7-5.8%), vitamin C (22.8-27 mg/100 g), anthocyanins (25.1-29.6 mg/100 g), and flavonoids (0.5-2.6 mg/100 g). The fruits were found to contain valuable unsaturated fatty acids (35-60%), especially MUFAs with dominant oleic, elaidic, palmitic, and erucic acids and PUFAs (α-linolenic, eicosapentaenoic, and linoleic acids). MUFAs from the ω-9 group accounted for 12-18%, whereas the content of PUFAs from the ω-3 and ω-6 groups was in the range of 15-23 and 6-21%, respectively. Exogenous amino acids, accounting for 56-62%, were dominated by leucine, phenylalanine, and lysine. The following order of the total polyphenolic content was established in the fresh fruit juice from the analyzed cultivars: 'Pokusa' < 'Polana' < 'Polka'. The different antioxidant capacity assays used in the study confirmed the high antioxidant potential of the fruits and fresh juice from the three R. idaeus cultivars. This indicates that raspberry fruits can serve as a source of nutrients and can be used as a valuable supplement in a healthy human diet and a raw material in the pharmaceutical and cosmetic industries.

Acetyl-L-carnitine attenuates chronic ethanol-induced oxidative stress, ER stress and apoptosis in rat gastric tissue.

Consuming alcohol affects almost all organs. Acetaldehyde, formed as the main product as a result of alcohol metabolism, causes the production of free superoxide radicals when oxidized, and accordingly oxidative and apoptotic processes are triggered. There are studies showing that carnitine has effects on oxidative and apoptotic processes that occur in various conditions. However, the mechanisms showing the effects of L-carnitine on these effects of alcohol have not been fully elucidated. In our study, the effects of acetyl-L-carnitine administration on the molecular mechanisms of oxidative stress, endoplasmic reticulum stress and apoptotic parameters in gastric tissue of rats chronically exposed to alcohol were investigated. Hematoxylin-eosin staining was used for histopathological studies. Endoplasmic reticulum stress markers were detected with immunohistochemical staining and western blotting. Apoptotic index was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Total oxidant and antioxidant status were examined by ELISA. Our results showed that chronic alcohol administration caused a significant increase in TOS levels, an indicator of oxidative stress, the levels of ER-stress-associated proteins XBP1, GRP78 and CHOP, and % apoptotic index values in rat gastric tissues. Additionally, it was determined that acetyl-L-carnitine administration caused an improvement in those values. Based on our data, we can conclude that acetyl-L-carnitine has a tissue protective effect by scavenging free oxygen radicals and reducing ER stress-related proteins XBP1, GRP78 and CHOP and apoptosis in chronic ethanol administered rats, and that this natural antioxidant may be beneficial in the treatment of oxidative stress-induced diseases.

Identification of antioxidant peptides targeting Keap1−Nrf2−ARE pathway from in vitro digestion of pork sausage with partial substitution of NaCl by KCl

The Kelch-like ECH-associated protein 1 (Keap1)–nuclear factor erythroid 2–related factor 2 (Nrf2)–antioxidant response elements (ARE) pathway is one of the most important cellular defense mechanisms against oxidative stress. This study focuses on finding antioxidant peptides from in vitro digestion products of pork sausage with partial substitution of NaCl by KCl by virtual screening. Six antioxidant peptides, LIVGFPAYGH, DWWGSTVR, WNSLLIR, IVGFPAYGH, FDNLWDQGL, and LRSPSWDPF, could activate the Keap1–Nrf2–ARE pathway and protect cells from oxidative stress. DWWGSTVR exhibits the most robust activity among them. Further studies indicated that DWWGSTVR could increase the expression of many antioxidant enzymes by enabling the transfer of Nrf2 from the cytoplasm to the nucleus. In summary, these six peptides are proven to be Nrf2 activators and could be used as functional foods to prevent and treat various oxidative stress-induced diseases.

Comparative &lt;i&gt;in-vitro&lt;/i&gt; antioxidant studies of crude methanol extract and four solvent fractions of red cultivar &lt;i&gt;Allium cepa&lt;/i&gt; l. bulbs

Oxidative stress-induced disease conditions are on the increase and there is need for natural sources of antioxidant for relieving stress. The crude extract of Allium cepa L. has been well published as a potential natural source of antioxidant. But there is inadequate information on the antioxidant activities of fractionated extracts of the plant. The in-vitro antioxidant capacity of crude extract of red cultivar A. cepa bulbs and its four solvent fractions were studied and compared using Nitric oxide radical inhibitory assay (NORIA), FRAP and DPPH antioxidant models. The results of the three models revealed that the crude methanol extract exhibited very good antioxidant activities. However, with the aid of DPPH, the crude methanol extract, ethyl acetate and methanol fractions exhibited excellent antioxidant activities in comparison with ascorbic acid. Serial extraction did not make any of the fractionated extracts better than the crude extract of the red cultivar A. cepa bulbs. These results also showed that red cultivar A. cepa bulbs is a natural source of antioxidants and could serve as therapeutic agent in the prevention or slowing down of oxidative stress. Further studies are currently underway to identify the active component responsible for the observed antioxidant properties.

Potential Implications of Hyperoside on Oxidative Stress-Induced Human Diseases: A Comprehensive Review.

Hyperoside is a flavonol glycoside mainly found in plants of the genera Hypericum and Crataegus, and also detected in many plant species such as Abelmoschus manihot, Ribes nigrum, Rosa rugosa, Agrostis stolonifera, Apocynum venetum and Nelumbo nucifera. This compound exhibits a multitude of biological functions including anti-inflammatory, antidepressant, antioxidative, vascular protective effects and neuroprotective effects, etc. This review summarizes the quantification, original plant, chemical structure and property, structure-activity relationship, pharmacologic effect, pharmacokinetics, toxicity and clinical application of hyperoside, which will be significant for the exploitation for new drug and full utilization of this compound.

Anthocyanins-rich purple potato extract prevents low-grade chronic inflammation-associated metabolic disorders

Dietary polyphenols including anthocyanins possess strong antioxidant and anti-inflammatory properties, and are known to help reduce risks of oxidative stress-induced chronic diseases. However, their effects on various aspects of the gut microenvironment towards preventing the unhealthy diet-induced metabolic disorders are still not well understood. The present study aims to verify the in vitro antioxidant and anti-inflammatory effects of the anthocyanin-rich extracts of purple potato (PPE), using a lipopolysaccharide (LPS) and high-fat diet (HFD)-induced obesity C57/BL6J mouse model, and to examine the effects of PPE on LPS+HFD-impaired metabolic homeostasis and the underlying mechanisms. We found that PPE, especially at higher dose significantly improved the glucose and lipid metabolism, and reduced inflammation in the plasma and various tissues. It significantly improved intestinal barrier integrity, altered fecal metabolite profile and gut microbiota composition. Our findings provide new insights into the roles of highly-pigmented vegetable-derived anthocyanins in maintaining gut health and ameliorating metabolic syndrome.

Sıçanlarda Valproik Asite Bağlı Testis Hasarına Rutin Etkisinin Araştırılması

Valproic acid (VALP) is a drug used for many psychiatric diseases such as epilepsy. However, the use of VALP has potential side effects on various tissues, including the testicles. Rutin (RUT) is a flavonoid with protective effects against oxidative stress-induced diseases and lipid peroxidation. In this study, the protective effects of RUT against testicular damage caused by VALP were investigated. For this purpose, 35 male Spraque-Dawley rats weighing 220-250 g were used in the study. The rats were randomly divided into 5 groups as Control (physiological saline), RUT (100 mg/kg/bw), VALP, (500mg/kg/bw), VALP+RUT 50 (500 mg/kg/bw VALP+50 mg/kg/bw RUT), and VALP +RUT 100 (500 mg/kg/bw VALP+100 mg/kg/bw RUT). At the end of the RUT and VALP administrations, the rats were sacrificed and testicular tissues were taken to be used for biochemical and spermatological analyzes. According to the results of this study, the MDA level in the testicular tissues of the VALP group was found to be statistically higher than the other experimental groups (p

The Influence of Antioxidants on Oxidative Stress-Induced Vascular Aging in Obesity.

Obesity is a worldwide trend that is growing in incidence very fast. Adipose tissue dysfunction caused by obesity is associated with the generation of oxidative stress. Obesity-induced oxidative stress and inflammation play a key role in the pathogenesis of vascular diseases. Vascular aging is one of the main pathogenesis mechanisms. The aim of this study is to review the effect of antioxidants on vascular aging caused by oxidative stress in obesity. In order to achieve this aim, this paper is designed to review obesity-caused adipose tissue remodeling, vascular aging generated by high levels of oxidative stress, and the effects of antioxidants on obesity, redox balance, and vascular aging. It seems that vascular diseases in obese individuals are complex networks of pathological mechanisms. In order to develop a proper therapeutic tool, first, there is a need for a better understanding of interactions between obesity, oxidative stress, and aging. Based on these interactions, this review suggests different lines of strategies that include change in lifestyle to prevent and control obesity, strategies for adipose tissue remodelling, oxidant-antioxidant balance, inflammation suppression, and strategies against vascular aging. Some antioxidants support different lines of these strategies, making them appropriate for complex conditions such as oxidative stress-induced vascular diseases in obese individuals.

Effects of ginseng consumption on the biomarkers of oxidative stress: A systematic review and meta-analysis.

Oxidative stress (OS) is a key factor involved in the initiation and development of chronic diseases. Despite its widespread acceptance as an antioxidant, the effects of ginseng on OS in human clinical trials have not been comprehensively analyzed. Therefore, this study aimed to synthesize the results of previous randomized clinical trials (RCTs) examining the impact of ginseng consumption on OS indicators. PubMed, Web of Science, Scopus, and Cochrane databases were searched for articles on the effects of ginseng consumption on oxidative stress markers up to March 20, 2023. Standardized mean difference (SMD) and 95% confidence intervals (CIs) were used to assess effect sizes. Twelve RCTs with 15 effect sizes revealed that the effects of ginseng lowered serum malondialdehyde (MDA) levels (SMD = 0.45, 95% CI: -0.87, -0.08; p = 0.03) and significantly increased the serum total antioxidant capacity (TAC) (SMD = 0.23, 95% CI: 0.01, 0.45; p = 0.04), oxidative dismutase (SOD) (SMD = 0.39, 95% CI: 0.21, 0.57; p < 0.0001), glutathione (GSH) (SMD = 0.36; 95% CI: 0.11, 0.61; p = 0.005), and glutathione reductase (GR) (SMD = 0.56; 95% CI: 0.31, 0.81; p < 0.0001) levels compared to the effects of placebo. However, the effects on serum glutathione peroxidase (GPx) and catalase (CAT) were not significant. Moreover, subgroup analysis based on intervention duration showed that ginseng consumption increased GPx (SMD = 0.91, 95% CI: 0.05, 1.78; p = 0.039) and CAT (SMD = 0.74, 95% CI: 0.27, 1.21; p = 0.002) levels after more than 4 weeks of intervention. According to the results of this meta-analysis, ginseng supplementation dramatically reduced MDA levels and increased TAC, SOD, GSH, and GR levels. Our results open up a new line of defense against oxidative stress-induced diseases.

The Potential of Cylindromatosis (CYLD) as a Therapeutic Target in Oxidative Stress-Associated Pathologies: A Comprehensive Evaluation.

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.

Clinical Relevance of lncRNA and Mitochondrial Targeted Antioxidants as Therapeutic Options in Regulating Oxidative Stress and Mitochondrial Function in Vascular Complications of Diabetes.

Metabolic imbalances and persistent hyperglycemia are widely recognized as driving forces for augmented cytosolic and mitochondrial reactive oxygen species (ROS) in diabetes mellitus (DM), fostering the development of vascular complications such as diabetic nephropathy, diabetic cardiomyopathy, diabetic neuropathy, and diabetic retinopathy. Therefore, specific therapeutic approaches capable of modulating oxidative milieu may provide a preventative and/or therapeutic benefit against the development of cardiovascular complications in diabetes patients. Recent studies have demonstrated epigenetic alterations in circulating and tissue-specific long non-coding RNA (lncRNA) signatures in vascular complications of DM regulating mitochondrial function under oxidative stress. Intriguingly, over the past decade mitochondria-targeted antioxidants (MTAs) have emerged as a promising therapeutic option for managing oxidative stress-induced diseases. Here, we review the present status of lncRNA as a diagnostic biomarker and potential regulator of oxidative stress in vascular complications of DM. We also discuss the recent advances in using MTAs in different animal models and clinical trials. We summarize the prospects and challenges for the use of MTAs in treating vascular diseases and their application in translation medicine, which may be beneficial in MTA drug design development, and their application in translational medicine.