The utilization of natural waxes to form oleogels has emerged as a new and efficient technique for structuring liquid edible oil into solid-like structures for diverse food applications. The objective of this study was to investigate the interaction between sunflower wax (SW) and monoglycerides (MGs) in olive oil oleogels and to assess their physical characteristics and storage stability. To achieve this, pure SW and a combination of SW with MGs in a 1:1 ratio were examined within a total concentration range of 6-12% w/w. The formed oleogels were characterized based on their microstructure, melting and crystallization properties, textural characteristics, and oxidative stability during storage. All the oleogels were shelf-stable, and as the concentration increased, the hardness of the oleogels also increased. The crystals of SW oleogels were long needle-like, while the combination of SW and MGs led to the formation of crystal aggregates and rosette-like crystals. The differential scanning calorimetry and FTIR showed that the addition of MGs led to different crystal structures. The oxidation results revealed that oleogels had low peroxide and TBARS values throughout the 28-day storage. These results provide useful insights about the utilization of SW and MGs oleogels for potential applications in the food industry.

Aspalathin (ASP) can protect H9c2 cardiomyocytes against high glucose (HG)-induced shifts in myocardial substrate preference, oxidative stress and apoptosis. While the protective mechanism of aspalathin remains unknown, nuclear factor (erythroid-derived 2)-like 2 (Nrf2) has emerged as a key factor for intracellular responses against oxidative stress. Therefore, we hypothesized that aspalathin protects the myocardium against hyperglycemia-induced oxidative damage by up-regulating Nrf2 expression in H9c2 cardiomyocytes and diabetic (db/db) mice. Using an oxidative stress RT2 Profiler PCR array, ASP at a dose of 1 µM was demonstrated to protect H9c2 cardiomyocytes against HG-induced oxidative stress, but silencing of Nrf2 abolished this protective response of ASP and exacerbated cardiomyocyte apoptosis. Db/db mice and their non-diabetic (db/+) littermate controls were subsequently treated daily for 6 weeks with either a low (13 mg/kg) or high (130 mg/kg) ASP dose. Compared to nondiabetic mice the db/db mice presented increased cardiac remodeling and enlarged left ventricular wall that occurred concomitant to enhanced oxidative stress. Daily treatment of mice with ASP at a dose of 130 mg/kg for 6 weeks was more effective at reversing complications than both a low dose ASP or metformin, eliciting enhanced expression of Nrf2 and its downstream antioxidant genes. These results indicate that ASP maintains cellular homeostasis and protects the myocardium against hyperglycemia-induced stress through activation of Nrf2 and its downstream target genes.

The biological aging, characterized by changing in metabolism and physicochemical properties of cells, has an impact on public health. Environment and lifestyle including factors like diet and physical activity seems to play a key role in healthy ageing. Several studies have shown that regular physical activity can enhance antioxidant defence mechanisms, including the activity of enzymes such as superoxide dismutase (SOD), catalase, and glutathione peroxidase. However, intense or prolonged exercise can also lead to an increase in ROS production temporarily, re-sulting in oxidative stress. This phenomenon is referred as "exercise-induced oxidative stress". The relationship between physical activity and oxidative stress in aging is complex and depends on various factors such as the type, intensity, duration, and frequency of exercise, as well as in-dividual differences in antioxidant capacity and adaptation to exercise. In this review, we ana-lyzed what is reported from several authors regarding the role of physical activity on oxidative stress in aging process as well as the role of hormesis and physical exercise as tools for preven-tion and treatment of sarcopenia, an aging related disease. Finally we reported what has recently been studied in relation to the effect of physical activity and sport on aging in women

This study presents a preliminary analysis of the chemical and thermal fuel properties of Afuze (AFZ) coal extracted from coalfields in Owan East Local Government Area of Edo State, Nigeria. The chemical properties of AFZ were examined by combined scanning electron microscopy-energy dispersive X-ray (EDX), whereas the thermal properties were deduced by thermogravimetric analysis (TGA) under flash (50 °C/min heating rate) oxidative (combustion) and non-oxidative (pyrolysis) conditions. The microstructure and morphology analysis of AFZ revealed has a compact structure comprising small-to-large, irregular shaped and exfoliated grains with a vitreous appearance typically ascribed to metal elements (Ti and Fe) kaolinite, quartz, and other clay minerals. Chemical analysis revealed carbon, oxygen, aluminium, silicon, sulphur, calcium, titanium, and iron in major and minor (trace) quantities. Thermal analysis under oxidative and non-oxidative conditions revealed degradation occurs in three stages, namely; drying or demineralisation, devolatilization or maceral degradation and the formation of char/coke or ash. Lastly, the findings showed that the temperature range for the oxidative thermal degradation process (338.58 - 756.76 °C) was higher than the non-oxidative process (378.43 - 615.34 °C). This observation can be explained by the exothermic nature of the oxidative (combustion) process, which ensures greater heat supply required to thermally soften or degrade the maceral coal components. Overall, the oxidative process yielded the residual mass (RM = 21.97%) and mass loss (ML = 78.03%). The lower ML (49.03%) but higher RM (50.97%) observed during non-oxidative degradation of AFZ could be ascribed to the largely endothermic nature of the process.

Probiotic feed additives have attracted considerable research interest in recent years because the effectiveness of probiotics can differ across microbial strains and the supplemented macroorganisms. The present study was conducted on 16 lambs divided into two groups (C - control and E - experimental). The examined lambs were aged 11 days at the beginning of the experiment and 40 days at the end of the experiment. The diet of group E lambs was supplemented with a multi-strain probiotic formulation (Lactobacillus plantarum AMT14, Lactobacillus plantarum AMT4, Lactobacillus rhamnosus AMT15, and Bifidobacterium animalis AMT30), whereas group C lambs did not receive the probiotic additive. At the beginning of the experiment (day 0) and on experimental days 15 and 30, blood was sampled from the jugular vein to determine and compare: phagocytic activity (PHAGOTEST) and oxidative metabolism (PHAGOBURST) of peripheral blood granulocytes and monocytes by flow cytometry. An analysis of the phagocytic activity of granulocytes and monocytes revealed significantly higher levels of phagocytic activity (expressed as the percentage of phagocytic cells and mean fluorescence intensity) in lambs administered the multi-strain probiotic formulation than in the control group. The probiotic feed additive also exerted a positive effect on the oxidative metabolism of both granulocytes and monocytes (expressed as the percentage of oxidative metabolism and mean fluorescence intensity) after stimulation with Escherichia coli bacteria and with PMA (4-phorbol-12-β-myristate-13-acetate).

There is little doubt that the efficacy of MnDPDP and its therapeutic improved counterpart Ca4Mn(DPDP)5 mainly depends on their MnSOD-mimetic activity when it comes to their potential use as rescue medicines, during e.g., acute myocardial infarction. However, pharmacokinetic considerations suggest that the efficacy of MnDPDP on Pt2+-associated neurotoxicity depends on another action of this drug. Electron Paramagnetic Resonance (EPR) studies have demonstrated that Pt2+ outcompetes Mn2+ and endogenous Zn2+ from binding to fodipir (DPDP), and hence suggest that the previously reported CIPN protective efficacy of MnDPDP is a result of chelation and elimination of Pt2+ by DPDP, which in turn suggests that Mn2+ is unnecessary for efficacy when it comes to oxaliplatin-associated CIPN.

This general review assesses the impact of physical exercise on oxidative and nitrosative stress and the counteractive role of antioxidants, drawing from a systematic literature search up to March 2024 in databases like PubMed and Web of Science. The review highlights studies on the effect of exercise on the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) and antioxidant responses in both human and animal models based on rigorous inclusion and exclusion criteria. Due to the variety of exercise types and participants' characteristics, a narrative synthesis approach was adopted. The findings indicate that moderate exercise boosts antioxidant defenses, known as hormesis, whereas excessive physical activity may increase oxidative and nitrosative damage. The review also explores the complex effects of antioxidant supplementation, revealing that while natural dietary antioxidants support health, high-dose supplements could potentially hinder positive adaptations to exercise. Recommendations for athletes and the general active population highlight the importance of balancing exercise and dietary intake to optimize health benefits. The review concludes with a call for more detailed research on tailored exercise and nutrition plans to dissect these intricate relationships further.

Hypertensive diseases of pregnancy (HDP) represent a global clinical challenge, affecting 5-10% of women and leading to complications for both maternal well-being and fetal development. At the heart of these complications is endothelial dysfunction, with oxidative stress emerging as a pivotal causative factor. The reduction in nitric oxide (NO) bioavailability is a vital indicator of this dysfunction, culminating in blood pressure dysregulation. In the therapeutic context, although antihypertensive medications are commonly used, they come with inherent concerns related to maternal-fetal safety, and a percentage of women do not respond to these therapies. Therefore, alternative strategies that directly address the pathophysiology of HDP are required. This article focuses on the potential of the nitrate-nitrite-NO pathway, abundantly present in dark leafy greens and beetroot, as an alternative approach to treating HDP. The objective of this review is to discuss the prospective antioxidant role of nitrate. We hope our discussion paves the way for using nitrate to improve endothelial dysfunction and control oxidative stress, offering a potential therapy for managing HDP.

Fetal Alcohol Spectrum Disorders (FASD) represent a continuum of lifelong impairments resulting from prenatal exposure to alcohol, with significant global impact. The “spectrum” of disorders includes a continuum of physical, cognitive, behavioral, and developmental impairments, which can have profound and lasting effects on individuals throughout their lives impacting their health, social interactions, psychological well-being and every aspect of their lives. This narrative paper explores the intricate relationship between oxidative stress and epigenetics in FASD pathogenesis and its therapeutic implications. Oxidative stress, induced by alcohol metabolism, disrupts cellular components, particularly in the vulnerable fetal brain, leading to aberrant development. Furthermore, oxidative stress is implicated in epigenetic changes, including alterations in DNA methylation, histone modifications, and microRNA expression, which influence gene regulation in FASD patients. Moreover, mitochondrial dysfunction and neuroinflammation contribute to epigenetic changes associated with FASD. Understanding these mechanisms holds promise for targeted therapeutic interventions. This includes antioxidant supplementation and lifestyle modifications to mitigate FASD-related impairments. While preclinical studies show promise, further clinical trials are needed to validate these interventions' efficacy in improving clinical outcomes for individuals affected by FASD. This comprehensive understanding of the role of oxidative stress on epigenetics in FASD underscores the importance of multidisciplinary approaches for diagnosis, management, and prevention strategies. Continued research in this field is crucial for advancing our knowledge and developing effective interventions to address this significant public health concern.

Type 2 diabetes mellitus (T2DM) accounts for one-sixth of deaths, globally, whereas cancer is the second leading cause of death in the U.S. T2DM is a known risk factor for many cancers. This review examines the link of Reactive oxygen Species (ROS)-altered metabolic and signaling pathways in T2DM to cancer. These reprogrammed metabolic and signaling pathways are activated that contribute to diabetic complications, impact redox balance (Oxidative Stress), and have differential roles in early and late stages of cancer. If the respiratory chain is highly reduced (as under hyperglycemic conditions) or if reduced cofactors accumulate, ROS are greatly elevated. ROS may cause mutations in mitochondrial DNA (mtDNA) that result in further ROS elevation. Amplification of ROS results in activation of PKC, an overarching signaling pathway that activates MAPK with subsequent regulation of several factors that result in pathophysiological manifestations of T2DM and cancer. Upregulation of PKC leads to deregulation of NF-kß that regulates the PKB/P13/Akt pathway that orchestrates cell survival, growth, proliferation, and glucose metabolism manifested in cancer. It also affects Insulin Receptor Substrate (IRS-1), decreasing insulin stimulated glucose transport and glucose uptake, disrupting subsequent cell signaling pathways contributing to the development of T2DM. Dyslipidemia is a hallmark of T2DM and cancer. ROS-induced lipid peroxidation leads to systemic inflammation, producing inflammatory prostaglandins, cytokines and chemokines that result in tumor proliferation, rapid tumor growth, and modulation of immunity. The dual role of ROS in early and late stages of cancer make antioxidant therapy precarious and may be responsible for controversial results. A system that delivers an antioxidant directly to mitochondria may be useful in inhibiting formation of ROS early during the pre-diabetic stage whereas antioxidant therapy must be halted in later stages to retard metastasis.

Recent years have seen an increased interest in the role of oxidative stress (OS) in pregnancy. Pregnancy inherently heightens susceptibility to OS, a condition fueled by a systemic inflam-matory response which culminates in an elevated presence of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in the circulatory system. The amplified OS in pregnancy can trigger a series of detrimental outcomes such as underdevelopment, abnormal placental function, and a host of pregnancy complications, including pre-eclampsia, embryonic resorp-tion, recurrent pregnancy loss, fetal developmental anomalies, intrauterine growth restriction, and in extreme instances, fetal death. The body’s response to mitigate the uncontrolled increase in RNS/ROS levels involves trace elements that take part in non-enzymatic and enzymatic defense mechanisms, namely, copper (Cu), zinc (Zn), manganese (Mn), iron (Fe), and selenium (Se). Determination of ROS concentrations poses a challenge due to their short lifespan, prompting the use of marker proteins, including malondialdehyde (MDA), superoxide dis-mutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), lipid peroxidation (LPO), catalase (CAT), and glutathione (GSH). These markers, indicative of redox stress intensity, can offer indirect assessments of pregnancy complications. Given the limitations in conducting experimental studies on pregnant women, animal models serve as valuable substitutes for in-depth research. This review delves into the mechanism of OS in pregnancy and underscores the pivotal role of markers in its evaluation.

Background/Objectives: Vitamin B12 deficiency can cause variable symptoms, which may be irreversible if not diagnosed and treated in a timely manner. We aimed to develop a widely accepted expert consensus to guide the practice of diagnosing and treating B12 deficiency. Methods: We conducted a scoping review of the literature published in PubMed since January 2003. Data were used to design a two-round Delphi survey to study the level of consensus among 42 experts. Results: The panelists agreed on the need for educational and organizational changes in the current medical practices for diagnosing and treating B12 deficiency. Recognition of clinical symptoms should receive the highest priority in establishing the diagnosis. There is agreement that the serum B12 concentration is useful as a screening marker, whereas methylmalonic acid or homocysteine can support the diagnosis. Patient lifestyle, disease history and medications can provide clues to the cause of B12 deficiency. Regardless of the cause of the deficiency, initial treatment with parenteral B12 was regarded as the first choice for patients with acute and severe manifestations of B12 deficiency. The use of high-dose oral B12 at different frequencies may be considered for long-term treatment. Prophylactic B12 supplementation should be considered for specific high-risk groups. Conclusions: There is a consensus that clinical symptoms need to receive more attention in establishing a diagnosis. B12 laboratory markers can support the diagnosis. The severity of clinical symptoms, the causes of B12 deficiency and the treatment goals govern decisions regarding the route and dose of B12 therapy.

Ferroptosis is a recent form of non-apoptotic cell death, which occurs due to imbalance of iron homeostasis (iron overload). Oxidative stress due to the impairment of the antioxidant system is a major pathophysiology during ferroptosis, which eventually results in lipid peroxidation. The cellular and physiological biomarker of ferroptotic cell death includes major alteration in the glutathione peroxidase 4 (GPX4) antioxidant system and lipid peroxidation induced loss of plasma membrane integrity. This review elaborates the mechanism of oxidative stress which triggers ferroptosis.

Different organisms, cell types, and even similar cell lines can dramatically differ in resistance to genotoxic stress. This testifies to the wide opportunities for genetic and epigenetic regulation of stress resistance. These opportunities could be used to increas the effectiveness of cancer therapy, develop new varieties of plants and animals, and search for new pharmacological targets to enhance human radioresistance, for example, for -manned deep space expeditions. Based on the comparison of transcriptomic studies in cancer cells, in this review we propose that there is a high diversity of genetic mechanisms of development of genotoxic stress resistance. This review focused onpossibilities and limitations of the proposed regulation of the resistance of normal cells whole organisms to genotoxic and oxidative stress by overexpressing of stress-response genes. Moreover, the existing experimental data on the effect of such overexpression on the resistance of cells and organisms to various genotoxic agents has been analyzed and systematized. We suggest that the recent advances in the development of multiplex and highly customizable gene overexpression technology that utilizes the mutant Cas9 protein and the wealth of available data on gene functions and their signal networks open new opportunities for research in this field.

Cancer being a multi-factorial disease, a multi-target approach is needed to treat it with minimal side-effects. Therefore, combined use of a proven herbal formula with chemo-therapy could be the better therapeutic. It may maintain homeostasis by synergistically targeting multiple signaling pathways involved in tumorigenesis, thus circumventing recurrence, resistance, and immunosuppression. Here we aim to determine the effectiveness and safety of an FDA-approved herbal formula, SR033 in combination with 5-fluorouracil (5FU) and paclitaxel (PTX). We report chemo-sensitization and chemo-synergy in HeLa and MCF-7 cell lines, immunomodulation of COX-2, PD-L1, VEGF and TGFβ and overall survival in-vitro and in-vivo via oral and topical delivery of SR033. In-vitro, SR033/5FU significantly reverses 5FU and PTX-resistance, lower COX-2, and PD-L1, resulting in TGFβ/ VEGF axis modulation. Furthermore, the study suggests that due to anti-oxidative potential of SR033, oral administration exerts chemo-preventive activity and restores cellular compartment in solid tumor and ascites-bearing mice models. Furthermore, the topical application, SR033L with low-dose 5FU increases survival rate, reduces tumor growth, and completely restores local and peripheral neutrophil-lymphocyte ratio in solid tumor mice model. The study indicates that SR033 could be a strong candidate in combination with low-dose 5FU and PTX for a holistic approach to cancer management.

Cells that experience high levels of oxidative stress respond with the induction of antioxidant proteins through the activation of the transcription factor Nrf2. Nrf2 is negatively regulated by Keap1 which binds to Nrf2 to facilitate its ubiquitination and ensuing proteasomal degradation under basal conditions. Here, we study protein folding and misfolding in Nrf2 and Keap1 in yeast, mammalian cells, and purified proteins under oxidative stress conditions. Both Nrf2 and Keap1 are susceptible to protein misfolding and inclusion formation upon oxidative stress. We propose that the intrinsically disordered regions within Nrf2 and the high cysteine content of Keap1 contribute to their oxidation and the ensuing misfolding. Our work reveals previously unexplored aspects of Nrf2 and Keap1 regulation and dysregulation by oxidation-induced protein misfolding.

Excretory-secretory products (ESPs) are the main research targets for investigating the hosts and helminths interaction. Parasitic worms can migrate to parasitic sites and avoid the host immune response by secreting this product. Angiostrongylus cantonensisis an important food-borne zoonotic parasite that causes severe neuropathological damage and symptoms, including eosinophilic meningitis or meningoencephalitis in humans. Benzaldehydes are organic compounds composed of a benzene ring and formyl substituents. This compound has anti-inflammatory and antioxidation properties. Previous studies showed that 3-hydroxybenzaldehyde (3-HBA) and 4-hydroxybenzaldehyde (4-HBA) can reduce apoptosis in A. cantonensis ESPs treated astrocytes. These results on the protective effect underlying benzaldehyde have primarily focused on cell survival. The study was designed to investigate the molecular mechanisms of endoplasmic reticulum stress (ER stress) and oxidative stress in astrocytes in A. cantonensis ESPs treated astrocytes and to evaluate the therapeutic consequent of 3-HBA and 4-HBA. First, we initially established the RNA-seq dataset in each group, including Normal, ESPs, ESPs+3-HBA, and ESPs+4-HBA. We also found that benzaldehyde (3-HBA and 4-HBA) can stimulate astrocytes to express ER stress-related molecules after ESP treatment. The level of oxidative stress could also be decreased in astrocytes by elevating antioxidant activity and reducing ROS generation. These results suggested that benzaldehyde may be a potential therapeutic compound for human angiostrongyliasis to support brain cell survival by inducing the expression levels of ER stress- and oxidative stress-related pathway.

It is now well accepted that most chronic diseases have a common feature which is “low-grade” inflammation. Whether inflammation is causal or rather consequent to these diseases is still a matter of debate. A key factor of inflammation is considered to be “oxidative stress”, which is the result of an alteration of redox homeostasis which is critical for the regulation of physiological cell and organ metabolism and proliferation. The term “oxidative stress” is how-ever often used in an inappropriate manner as the primary target of the initial oxidative radical, superoxide ion, is nitric oxide which, being in large excess, acts as a “buffer”, yielding reactive nitrogen species. It is only once the superoxide fluxes exceed the nitric oxide fluxes that true “oxidative stress” occurs. Nitro-oxidative stress is a more appropriate term which takes into account the evolving generation of reactive nitrogen and oxygen species and their effects on cell and organ pathophysiology. The molecular bases of redox homeostasis and nitro-oxidative stress will be presented and discussed using obesity-linked inflammation as a path-ophysiological example.

Sickle cell disease (SCD) is the most common hereditary disorder of hemoglobin (Hb) that affects approximately a millions people worldwide. It is characterized by a single nucleotide substitution on the β-globin gene, leading to the production of abnormal sickle hemoglobin with multi-system consequences. Mutated Hb leads to profound changes in: i) red blood cell metabolism and physiology; ii) endothelial signaling; and iii) immune response. Oxidative stress is an important hallmark of SCD. It plays a key role in the pathophysiology of hemolysis, vessel occlusion and the following organ damage in sickle cell patients. For this reason, reactive oxidizing species and the (end)-products of their oxidative reactions have been proposed as markers of both tissue pro-oxidant status and disease severity. Although more studies are needed to clarify their role, antioxidant agents have been shown to be effective in reducing pathological consequences of the disease by preventing oxidative damage in SCD, i.e. by decreasing the oxidant formation or repairing the induced damage. An improved understanding of oxidative stress will lead to targeted antioxidant therapies that should prevent or delay the development of organ complications in this patient population.

The objective of this study was to investigate age-related changes in cashmere production and the population of active secondary hair follicles in cashmere goats across different age groups, as well as to explore the association between secondary hair follicle activity and oxidative stress. A total of 104 adult Inner Mongolian ewe goats, aged between 2 and 7 years old, were randomly selected as experimental subjects. Skin samples were collected in August 2020 and cashmere samples were collected in April 2021. The cashmere fiber yield, staple length, and diameter showed age-related variations in cashmere goats aged 2 to 7 years (P < 0.05). Cashmere production was higher in goats aged 2-4 years compared to those aged 5-7 years (P < 0.05). There were no significant differences in the population of primary and secondary hair follicles among goats aged 2 to 7 years. However, the population of active secondary hair follicles varied significantly with age, with the younger group (aged 2-4 years) having a higher population than those aged 5 – 7 years (P < 0.05). A moderate negative correlation was observed between cashmere fiber diameter and the population of active secondary hair follicles (P < 0.05). Age-related variations in skin antioxidant capacity and oxidative damage were observed among cashmere goats aged 2 to 7 years old (P < 0.05). Goats aged 2 to 4 years exhibited higher antioxidant capacity and lower oxidative damage (P < 0.05). Interestingly, the skin antioxidant capacity and oxidative damage exhibited significant positive and negative correlations, respectively, with the population of active secondary hair follicles (P < 0.05). This study presents a novel approach to enhance the activity of secondary hair follicles and improve cashmere production performance through the regulation of oxidative stress.

Aging is associated with an increasing dysfunction of key brain homeostasis mechanisms and represents the main risk factor across most neurodegenerative disorders. However, the degree of dysregulation and the affectation of specific pathways set apart normal aging from neurodegenerative disorders. In particular, the neuronal metabolism of catecholaminergic neurotransmitters appears to be a specifically sensitive pathway that is affected in different neurodegenerations. In humans, catecholaminergic neurons are characterized by an age-related accumulation of neuromelanin (NM), rendering the soma of the neurons black. This intracellular NM appears to serve as a very efficient quencher for toxic molecules. However, when a neuron degenerates, NM is released together with its load (many undegraded cellular components, transition metals, lipids, antibiotics) contributing to initiate and worsen an eventual immune response, exacerbating the oxidative stress, ultimately leading to the neurodegenerative process. This review focuses on the analysis of the role of NM in normal aging and catecholaminergic metabolism due to its capability as a pro-oxidant and other harmful molecules, versus its involvement in oxidative stress and aberrant immune response, which it is highly dependent on NM saturation state and its extracellular release.

This review focuses on the role of small extracellular vesicles in the pathophysiological mechanisms of retinal degenerative diseases. Many of these mechanisms are related or modulated by the oxidative burden of the retinal cells. It has been recently demonstrated that cellular communication in the retina involves extracellular vesicles and that their rate of release and cargo features might be affected by the cellular environment and in some instances also mediated by autophagy. The fate of these vesicles is diverse, and could end up in the circulation and be used as markers, or target neighbour cells modulating gene and protein expression and eventually also angiogenesis. Neovascularization in the retina promotes vision loss in diseases such as diabetic retinopathy and age-related macular degeneration. The importance of micro RNAs, either as small extracellular vesicles’ cargo or free circulating, on the regulation of retinal angiogenesis is also discussed.

Radical oxygen species formed in human tissue cells by many endogenous and exogenous pathways, cause extensive oxidative damage, which has been linked to various human diseases. This review paper provides an overview of lipid peroxidation and focuses on the free-radicals initiated processes of LDL oxidative modification and DNA oxidative damage, which are widely associated to the initiation and development of atherosclerosis and carcinogenesis, respectively. The article subsequently provides an overview of the recent human trials or even in vitro investigations on the potential of natural antioxidant compounds (such as carotenoids, vitamins C and E) to monitor LDL and DNA oxidative changes.

Background: Fullerenes and metallofullerenes can be considered promising nanopharmaceuticals themselves and as a basis for chemical modification. As reactive oxygen species homeostasis plays a vital role in cells, the study of their effect on genes involved in oxidative stress and anti-inflammatory response is of particular importance. Methods: Human fetal lung fibroblasts were incubated with aqueous dispersions of C60, C70, and Gd@C82 in concentrations of 5 nM and 1.5 µM for 1, 3, 24, and 72 hours. Cell viability, intracellular ROS, NOX4, NFκB, PRAR-γ, NRF2, heme oxygenase 1, and NAD(P)H quinone dehydrogenase 1 expression have been studied. Results &amp; conclusion: The aqueous dispersions of C60, C70, and Gd@C82 fullerenes are active participants in ROS homeostasis. Low and high concentrations of AFDs have similar effects. C70 was the most inert substance, C60 was the most active substance. All AFDs have both a “prooxidant” and “antioxidant” effect, but with a different balance. Gd@C82 was a substance with more pronounced antioxidant and anti-inflammatory properties, while C70 had more pronounced “prooxidant” properties.

In this study, we have focused on studying the heterogenous degradation kinetics of regarding the decomposition of emergency contraceptive agent levonorgestrel (LNG), which is a second-generation synthetic progestogen that is the active component of the racemic mixture of norgestrel. The degradation processes of the active pharmaceutical ingredient (API) were compared with the ones obtained from model system containing the API along with the excipients that are found in a commercialized pharmaceutical formulation in a mass ratio of 1:1 (LNGMIX), in order to observe if the excipients have a stabilizing or destabilizing effect for the degradation of this progestogen. To achieve this, the following investigational methods were used: FTIR (Fourier transform infrared) spectroscopy and thermal analysis (TG/DTG/DSC analysis). For the kinetic analysis the data obtained from two main decomposition processes observed on the DTG curves were used and processed with a preliminary method, namely ASTM E698 and two isoconversional methods: Friedman and Flynn-Wall-Ozawa. The isoconversional study revealed that the decomposition mechanism of both LNG and LNGMIX are complex, and the excipients have a stabilizing effect over decomposition of API in tablet.

Many signaling pathways, molecular and cellular actors which are critical for wound healing have been implicated in cancer metastasis. These two conditions are a complex succession of cellular biological events and accurate regulation of these events is essential. Apart from inflammation, macrophages-released ROS arise as major regulators of these processes. But, whatever the pathology concerned, oxidative stress is a complicated phenomenon to control and requires a finely tuned balance over the different stages and responding cells. This review provides an overview of the pivotal role of oxidative stress in both wound healing and metastasis, encompassing the contribution of macrophages. Indeed, macrophages are major ROS producers but also appear as their targets since ROS interfere with their differentiation and function. Elucidating ROS functions in wound healing and metastatic spread may allow the development of innovative therapeutic strategies involving redox modulators.

ADHD, one of the most prevalent diseases during childhood, we still do not know its precisely origin, although oxidative/nitrosative stress and the hypothalamic-pituitary-adrenal axis are suggested contributors. Methylphenidate, among others, is the main drug used in these patients, but its effects on relevant markers and structures remain unclear. This study, involving 59 patients diagnosed with ADHD according to DSM-5 criteria, aimed to assess changes in cortisol levels (using cortisol awakening response, CAR) and oxidative/nitrosative status with the treatment. Blood samples before and 3 months after treatment with methylphenidate were used to measure oxidative and inflammatory markers, and the endogenous antioxidant activity, while saliva samples tracked cortisol awakening response (CAR). The results show a treatment-related improvement in the redox profile, with the reduction of advanced oxidation protein products (AOPP), lipid peroxidation (LPO), and nitrite plus nitrate (NOx) levels, and the increase of the enzymatic activities of glutathione reductase (GRd) and catalase (CAT). Moreover, the area under the curve (AUC) of CAR increased significantly, indicating increased reactivity of the HPA axis. These result support by the first time the involvement of the endogenous antioxidant system in the pathophysiology of ADHD.

Genetic, developmental, biochemical, and environmental variables interact intricately to produce sex differences. The significance of sex differences in cancer susceptibility is being clarified by numerous studies. Epidemiological research and cancer registries have revealed over the past few years that there are definite sex variations in cancer incidence, progression, and survival. However, oxidative stress and mitochondrial dysfunction also have a significant impact on the response to treatment of neoplastic diseases. Young women may be more protected from cancer than men because most of the proteins implicated in the regulation of redox state and mitochondrial function are under the control of sexual hormones. In this review, we describe how sexual hormones control the activity of antioxidant enzymes and mitochondria, as well as how they affect several neoplastic diseases. The molecular pathways that underlie the gender-related discrepancies in cancer that have been identified may be better understood, which may lead to more effective precision medicine and vital information on treatment options for both males and females with neoplastic illnesses.

Oxidative stress driven by several environmental and local airway factors associated with chronic obstructive bronchiolitis, a hallmark feature of COPD, plays a crucial role in the disease pathomechanism. Unbalance between oxidants and antioxidant defense mechanisms not only amplifies the local inflammatory processes, but it also worsens cardiovascular health and contribute to the COPD related cardiovascular dysfunctions and mortality. The current review summarizes recent developments in our understanding of different mechanisms contributing to oxidative stress and its countermeasures with special attention to those that link local and systemic processes. Major regulatory mechanisms orchestrating these pathways are also introduced together with some suggestions for further research on the field.

Introduction:In this study we evaluated the connivance of oxidative and antioxidative parameters in the pathogenesis of spinal cord injury (SCI). Although the etiology and pathogenesis of SCI remain to be fully understood, it has been suggested that reactive oxygen species (ROS) and oxidative stress may play a significant role in the pathophysiology of SCI. Furthermore, there is little information available in scientific literature about oxidative and antioxidative parameters in SCI patients. Methods:Oxidative stress was determined by measuring the levels of Lipid Peroxides (LPO) and Protein carbonyl in plasma and antioxidative parameters like Glutathione Reductase (GR), catalase and Glutathione peroxidase (GPx) in lysate in 40 SCI patients and 40 healthy subjects without SCI. However, pain was measured by McGill pain questionnaire. Results: Concentrations of catalase (p<0.01), GR (p<0.01) and GPx (p<0.01) were significantly lower in patients with SCI than in controls, and levels of oxidative stress parameters, LPO (p<0.01), Protein carbonyl (p<0.01) were significantly higher in patients than in controls. A significant positive correlation was found between LPO and pain score among SCI patients group. Furthermore, a significant positive correlation was also found between Protein carbonyl and pain score among SCI patients group than in control group. Conclusion: The present results indicate that SCI patients are exposed to oxidative stress and this escalated oxidative stress may play a role in the etiopathogenesis of the disease. Moreover, our results also show that increased oxidative stress parameters are more strongly amalgamated with pain in SCI patients.

Metal exposure has been associated with a wide range of adverse birth outcomes and oxidative stress is a leading hypothesis of the mechanism of action of metal toxicity. We assessed the relationship between maternal exposure to essential and non-essential metals and metalloids in pregnancy and oxidative stress markers, and sought to identify windows of vulnerability and effect modification by fetal sex. In our analysis of 215 women from the PROTECT birth cohort study, we measured 14 essential and non-essential metals in urine samples at three time points during pregnancy. The oxidative stress marker 8-iso-prostaglandin F2α (8-iso-PGF2α) and its metabolite 2,3-dinor-5,6-dihydro-15-15-F2t-IsoP, as well as prostaglandin F2α (PGF2α), were also measured in the same urine samples. Using linear mixed models, we examined the main effects of metals on markers of oxidative stress as well as the visit-specific and fetal sex-specific effects. After adjustment for covariates, we found that a few urinary metal concentrations, most notably cesium (Cs) and copper (Cu), were associated with higher 8-iso-PGF2α with effect estimates ranging from 7.3 to 14.9 % for each interquartile range, increase in the metal concentration. The effect estimates were generally in the same direction at the three visits and a few were significant only among women carrying a male fetus. Our data show that higher urinary metal concentrations were associated with elevated biomarkers of oxidative stress. Our results also indicate a potential vulnerability of women carrying a male fetus.

The mass concentration of particulate matter (PM) has been systematically used in epidemiological studies as exposure indicator, to relate airborne concentrations with a wide variety of human health effects, which can be hardly explained by using this single parameter. In fact, PM is a “particle cocktail” that includes a complex mixture of compounds with a wide range of sizes, chemical compositions and emission sources. Current research hypothesizes that many of the adverse health effects are derived from oxidative stress in biological systems caused by the deposition of PM into the lungs. This emerging hypothesis is called the oxidative stress paradigm. In this commentary article we analize how this new paradigm could help to answer the as-of-yet unanswered questions related to the mechanism of action of PM pollution on human health. Acellular oxidative potential (OP) assays have been emerged as a promising approach to quantify the PM potential to induce oxidative stress and to relate it with the chemical composition and size distribution of PM. Recent researches have shown that the OP is related to the presence of metals, organic carbon, polyaromatic hydrocarbons and quinones. However, the association between PM and particle-induced toxicity is still largely unknown. Therefore, additional research is needed to identify the specific PM characteristic(s), such as its specific size, emission source or chemical content, which contribute the most to its redox activity. Thus, the OP measurements provide information that allows us to evaluate and integrate the toxic potential of PM in a unique parameter, whose relationships with emission sources, size distribution and/or chemical composition should be faced in the near future.

Redox regulation and oxidative stress have become areas of major interest in spermatology. Alteration of redox homeostasis is recognized as a significant cause of male factor infertility and is behind the damage that spermatozoa experience after freezing and thawing or conservation in a liquid state. While for a long time, oxidative stress was just considered an overproduction of ROS, nowadays it is considered as a consequence of redox deregulation. Many essential aspects of spermatozoa functionality are redox regulated, with reversible oxidation of thiols in cysteine residues of key proteins acting as an “on-off” switch controlling spermatic function. However, if deregulation occurs, these residues may experience irreversible oxidation and oxidative stress leading to spermatic malfunction and ultimately death. Stallion spermatozoa are “professional producers” of ROS due to their intense mitochondrial activity, and thus sophisticated systems to control redox homeostasis are also characteristic of this species. As a result, combined with the fact that embryos can easily be collected in this species, horses are a good model for the study of redox biology in the spermatozoa and its impact on the embryo.

Chronic kidney disease (CKD) is a major non-communicable disease associated with high rates of premature morbidity and mortality. The prevalence of hypovitaminosis D (deficiency of 25(OH)D or 25D) is greater in racial/ethnic minorities and in patients with CKD than the general population. Low 25D is associated with bone and mineral disorders as well as immune, cardiometabolic and cardiovascular (CV) diseases. Thus, it has been suggested low 25D contributes to the poor outcomes in patients with CKD. The prevalence of hypovitaminosis D rises progressively with advancing severity of kidney disease with over 30% of patients with CKD stage 3 and 70% patients with CKD stage 5 estimated to have low levels of 25D. This report describes several of the abnormal physiologic and counter-regulatory actions related to low 25D in CKD such as those in oxidative stress and inflammatory systems, and some of the preclinical and clinical evidence or lack of thereof of normalizing serum 25D levels to improve outcomes in patients with CKD, and especially for the high risk subset of racial/ethnic minorities who suffer from higher rates of advanced CKD and hypovitaminosis D.

An accumulating body of evidence suggests that physiological reactive oxygen species (ROS) generated by NADPH oxidases act as a redox signal to re-establish homeostasis, a capacity that progressively declines during aging, but is maintained in long-lived animals to promote healthy aging. In the model organism Caenorhabditis elegans, ROS generated by dual oxidases (Duox) are important for extracellular matrix integrity, pathogen defense, oxidative stress resistance, and longevity. The Duox enzymatic activity is tightly regulated and under cellular control. Developmental molting cycles, pathogen infections, toxins, mitochondrial-derived ROS, drugs, and small GTPases (RHO-1) can activate Duox (BLI-3) to generate ROS, whereas NADPH oxidase inhibitors and negative regulators, such as MEMO-1, can inhibit Duox to generate ROS. Three mechanisms-of-action have been discovered for the Duox/BLI-3-generated ROS: 1) enzymatic activity to catalyze cross-linking of free tyrosine ethyl ester in collagen bundles to stabilize extracellular matrices, 2) high ROS bursts/levels to kill pathogens, and 3) Redox signaling activating downstream kinase cascades to transcription factors orchestrating oxidative stress- and immunity responses to re-establish homeostasis. Although Duox function at the cell surface is well established, recent genetic and biochemical data also suggests a novel role for Duoxs at the endoplasmic reticulum membrane to control redox signaling. Evidence underlying these mechanisms initiated by ROS from NADPH oxidases and their relevance for human aging are discussed in this review. Appropriately controlling NADPH oxidase activity for local and physiological redox signaling to maintain cellular homeostasis might be a therapeutic strategy to promote healthy aging.

Neurodegenerative diseases like Alzheimer’s disease (AD) are poised to become a global health crisis, and therefore understanding the mechanisms underlying the pathogenesis is critical for the development of therapeutic strategies. Mutations in genes encoding presenilin occur in most familial Alzheimer’s disease but the role of PSEN in AD is not fully understood. In this review, the potential modes of pathogenesis of AD are discussed, focusing on calcium homeostasis and mitochondrial function. Moreover, research using Caenorhabditis elegans to explore the effects of calcium dysregulation due to presenilin mutations on mitochondrial function, oxidative stress and neurodegeneration is explored.

Formidable and often seemingly insurmountable conceptual, technical, and methodological challenges hamper the measurement of oxidative stress in humans. For instance, fraught and flawed methods, such as the thiobarbituric acid reactive substances assay kits for lipid peroxidation, rate-limit progress. To advance translational redox research, we present ten comprehensive “cheat codes” for measuring oxidative stress in humans. The cheat codes include analytical approaches to assess reactive oxygen species, antioxidants, biomarkers of oxidative damage and redox regulation. They provide essential conceptual, technical, and methodological information inclusive of curated “do” and “don’t” guidelines. Given the biochemical complexity of oxidative stress, we present a research question-grounded decision tree guide for selecting the most appropriate cheat code (s) to implement in a prospective human experiment. Worked examples demonstrate the benefits of the decision tree-based cheat code selection tool. The ten cheat codes define an invaluable resource for measuring oxidative stress in humans.

Background: In military flight operations fighter pilots work during flights constantly under hyperoxic breathing conditions with supplemental oxygen in varying hypobaric environments. These conditions are suspected to cause oxidative stress to neuronal organ tissues. For civilian flight operations the Federal Aviation Administration (FAA) also recommends supplemental oxygen for flying under hypobaric conditions equivalent to higher than 3048m altitude and makes it mandatory for conditions equivalent of more than 3657m altitude. Aim: We hypothesized that hypobaric-hyperoxic civilian commercial and private flight conditions with supplemental oxygen in a flight simulation in a hypobaric chamber at 2500m and 4500m equivalent altitude would cause significant oxidative stress in healthy individuals. Methods: 12 healthy subjects (6m, 6f, mean age 35,7yrs) from a larger cohort were selected to perform a 3hrs flight simulation in a hypobaric chamber with increasing supplemental oxygen levels (35%,50%,60% and 100% FiO2 via venturi valve equipped face mask) switching back and force between simulated altitudes of 2500m and 4500m. Arterial blood pressure and oxygen saturation were constantly measured via radial catheter and blood samples for blood gases taken from the catheter at each altitude and oxygen level. Additional blood samples from the arterial catheter at baseline and 60% oxygen at both different altitudes were centrifuged inside the chamber and the serum frozen instantly at minus 21°Celsius for later analysis of the oxidative stress markers malondialdehyde low density lipoprotein (M-LDL) and glutathione-peroxidase (GLP) via elisa test. Results: 11 subjects finished the study without adverse events. Whereas PO2 levels increased in the mean with increasing oxygen levels from baseline 96.2 mmHg to 160.9 mmHg at 2500m altitude and 60% FiO2 and 113.2 mmHg at 4500m altitude and 60% FiO2, there was no significant increase in both oxidative markers from baseline to 60% FiO2 at these simulated altitudes. Some individuals had a slight increase, some not at all or even a slight decrease. A moderate correlation (Pearson correlation coefficient 0,55) existed between subject age and glutathione peroxidase levels at 60% FiO2 at 4500m altitude. Conclusion: Supplemental oxygen of 60% FiO2 in a flight simulation comparing to flying in cabin pressure levels equivalent to 2500m-4500m altitude does not lead to a significant increase or decrease in the oxidative stress markers M-LDL and GLP in serum of arterial blood.

Extracellular vesicles (EVs) released by different cell types play significant role in many physiological and pathophysiological processes. In physiological conditions red blood cells (RBCs) derived EVs compose 4 - 8% of all circulating EVs, and oxidative stress (OS) as a consequence of different pathophysiological conditions significantly increases the amount of circulated RBC-derived EVs, however the mechanisms of EV formation are not fully defined yet. To analyze OS-induced EV formation and RBCs transformations we used flow cytometry to evaluate cell esterase activity, caspase-3 activity, and band 3 clustering. Band 3 clustering was additionally analyzed by confocal microscopy. Two original laser diffraction-based approaches were used for analysis of cell deformability and band 3 activity. Hemoglobin species were characterized spectrophotometrically. We showed that cell viability in tert-butyl hydroperoxide-induced OS directly correlated with oxidant concentration to cell count ratio, RBCs-derived EVs contained hemoglobin oxidized to hemichrome (HbChr). OS induced caspase-3 activation and band 3 clustering in cells and EVs. Importantly, we showed that OS-induced EV formation is independent from calcium. Presented data indicated that during OS RBCs eliminate HbChr by vesiculation, in order to sacrifice the cell itself thereby prolonging lifespan and delaying the untimely clearance of in all other respects healthy RBCs.

The aim of this study was to find a correlation between in vivo NIR scan patterns, oxidative status, and blood serum metabolites in rabbits fed diets protected or unprotected against oxidation. Rabbits does in groups of eight were fed for 9 weeks with diets containing linseed, rich in polyunsaturated fatty acids (LS), or linseed plus hazelnut skins, with antioxidant function (LS+HS), and palm oil, rich in saturated fatty acids (PO). The animals were examined at days 1, 31, and 63 using a smart SCÏO molecular sensor, a new miniaturized web-based wireless device, applied to the internal ear flap (NIR range 740-1070 nm). The hazelnut peels integrated diet protected the rabbits from the oxidative stress induced by the addition of unprotected polyunsaturated fats. NIR tomoscopy was variously correlated with serum parameters, lysozyme (R2=0.71), ROMs (0.47), cholesterol (0.49), triglycerides (0.40), and a multivariate Index of Oxidative Risk (0.67 [IOR]). The correlations suggested a close connection between the clustering of the diets according to the laboratory variables and the NIRS scan pattern clustering at the ending trial day, as shown by the highly significant odds ratios. Advantageous use of this simple, painless technique was evident in the planning phase, with no difference among the groups at the beginning of the study, but an effect size that evolved differently over time until the end of the study. In a practical validation of the SCÏO model in 92 commercial rabbit does, the average spread of the predicted IOR was 33% in lactating does (2.54±0.05) vs. dry does (1.91±0.07).

Cardiotoxicity is the main side effect of several chemotherapeutic drugs. Doxorubicin (Doxo) is one of the most used anthracyclines in the treatment of many tumors, but the development of acute and chronic cardiotoxicity limits its clinical usefulness. Different studies focused only on the effects of long-term Doxo administration, but recent data show that cardiomyocyte damage is an early event induced by Doxo after a single administration that can be followed by progressive functional decline, that lead to overt heart failure. The knowledge of molecular mechanisms involved in the early stage of Doxo induced cardiotoxicity is of paramount importance to treat and/or prevent it. This review aims to illustrate several mechanisms considered to underlie Doxo-induced cardiotoxicity, such as oxidative and nitrosative stress, inflammation, and mitochondrial dysfunction. Moreover, here we report data from both in vitro and in vivo studies indicating new therapeutic possibilities to prevent Doxo-induced cardiotoxicity.

Atherosclerosis (AS) is an age-related disease. Mitochondria and telomere links have been considered to play important roles in AS. PinX1 is a potent and highly conserved endogenous telomerase inhibitor. However, the role of pinX1 in AS and its role in oxidative stress have not been reported. In order to investigate the role of pinX1 in AS, we established a classical AS mice model in the present work and increased pinX1 protein expression using pinX1 overexpression adeno-virus by tail vein injection. Then, red-oil O and HE staining were employed to evaluate the severity of AS. Serum lipid profile and oxidative stress were also detected by using its specific chemical testing kit. The results indicated that high-fat diet (HFD) markedly decreased pinX1 and increased p66shc protein expression, whereas overexpression of pinX1 protein expression in mice produced the opposite results. In addition, pinX1 significantly minimized plaque area and alleviated the abnormal serum lipid profile. By using Western blot and Biochemical assay kits, overexpression of pinX1 decreased p66shc and MMP-9 protein expression and reduced oxidative stress. This study showed pinX1 can inhibit p66shc, MMP-9, and related oxidative stress, pinX1 may be considered as a new candidate target for the treatment of AS.

Chrysoeriol (CHE) is a flavonoid substance that exists in many plants and has various physiological and pharmacological effects, including anti-inflammatory, antioxidant, anti-tumor, and protective activity, especially for the cardiovascular system and liver. This study aimed to analyze the results and possible mechanisms of CHE on early porcine embryo development. Adding CHE to the culture media can improve the development quality of early porcine embryos. CHE significantly increased the blastocyst rate and total cell number of embryos in vitro. The apoptosis of blastocyst in CHE-treated culture also decreased significantly compared with untreated culture. Furthermore, CHE downregulated intracellular reactive oxygen species (ROS) and increased glutathione (GSH) in embryos. CHE was also shown to improve the activity of mitochondria and inhibit the occurrence of autophagy. In addition, antioxidant-related genes (SOD1, SOD2, and CAT) and cell pluripotency-related genes (SOX2, OCT4, and NANOG) were upregulated, while those related to apoptosis (Caspase 3) and autophagy (LC3B) showed a downward trend after supplementation with CHE. These results indicated that CHE improved the development of porcine embryos in vitro by reducing oxidative stress and autophagy levels.

Specific aquaporins (AQP), called peroxyporins, play a relevant role in controlling H2O2 permeability and ensure reactive oxygen species wasting during oxidative stress. Another target involved in oxidative stress is the Sigma1 Receptor (S1R), since its activation is triggered by oxidative or endoplasmic reticulum stress. Herein we evaluated the effect of S1R modulators on AQP-dependent water permeability in the presence and in the absence of oxidative stress. Applying stopped-flow light scattering and fluorescent probe methods, water and hydrogen peroxide permeability in Hela cells have been studied. Results evidenced that S1R agonists can restore water permeability in heat-stressed cells and the co-administration with a S1R antagonist totally counteracted the ability to restore the water permeability. All compounds except one were able to counteract the oxidative stress of HeLa cells specifically knocked down for S1R. Taken together, our results support the hypothesis that the investigated compounds act as dual aquaporin and Sigma1 receptor (DAS) modulators. The finding that small molecules can modulate both AQP and S1R opens a new direction toward the identification of innovative drugs able to regulate cell survival during oxidative stress in pathologic conditions, like cancer and degenerative diseases.

This study aims to systematically review and meta-analyze the nitro-oxidative stress (O&NS)/antioxidant (ANTIOX) ratio in the peripheral blood of people with mild cognitive impairment (MCI). We searched PubMed, Scopus, Google Scholar, and Web of Science for articles published from inception until July 31, 2021. Forty-six studies on 3.798 MCI individuals and 6.063 healthy controls were included. The O&NS/ANTIOX ratio was significantly higher in MCI than in controls with a Standardized Mean Difference (SMD)=0.378 (95% CI: 0.250; 0.506). MCI individuals showed increased lipid peroxidation (SMD=0.774, 95%CI: 4.416; 1.132) and O&NS-associated toxicity (SMD=0.621, CI: 0.377; 0.865) and reduced glutathione (GSH) defenses (SMD=0.725, 95%CI: 0.269; 1.182) as compared with controls. MCI was also accompanied by significantly increased homocysteine (SMD=0.320, CI: 0.059; 0.581), but not protein oxidation, and lowered non-vitamin (SMD=0.347, CI: 0.168; 0.527) and vitamin (SMD=0.564, CI: 0.129; 0.999) antioxidant defenses. The results show that MCI is at least in part due to increased neuro-oxidative toxicity and suggest that treatments targeting lipid peroxidation and the GSH system may be used to treat or prevent MCI.

Beyond factors such as smoking and obesity, the risk of getting gastrointestinal cancer is passed down from parents to offspring, inherited by a gene mutation, predisposing them to develop cancer in their lifetime. Here we describe the clinical history of family members affected by gastrointestinal pathologies often leading to cancer. In the epidemiological study, the cohort of members of this family shared a high risk of developing gastrointestinal diseases. The subjects were monitored from May 2006 to December 2017 by collecting periodically clinical and endoscopic data, and determining both auto-modification of lymphocyte Poly(ADP-ribose)Polymerase as early signal of DNA damage, and erythrocyte membrane lipid composition (Fat Profile). Both biomarkers were demonstrated to be non invasive and easy tools, to monitor over time family members, first the oldest members (nine siblings), and thereafter their offspring, whose cell status evolved from physiological even to cancerous one. All subjects developed gastrointestinal pathologies of different kind and seriousness. Some diseases evolved to cancer, sometimes as a sudden and lethal event. The results of the two molecular approaches, agreed and even predicted the clinical and imaging paths. This cohort study supported the hypothesis that both noninvasive molecular analyses can predict altered cell states and support clinical and imaging tests.

The core pathological event in Parkinson’s disease (PD) is the specific dying of dopamine (DA) neurons of the substantia nigra pars compacta (SNc). Why SNc DA neurons are especially vulnerable and why idiopathic PD has only been found in humans is still puzzling. The two main underlying factors of SNc DA neuron vulnerability appear related to high DA production, namely (i) the toxic effects of cytoplasmic DA metabolism and (ii) continuous cytosolic Ca2+ oscillations in the absence of the Ca2+-buffer protein calbindin. Both factors cause oxidative stress by producing highly reactive quinones and increasing intra-mitochondrial Ca2+ concentrations, respectively. High DA expression in human SNc DA neuron cell bodies is suggested by the abundant presence of the DA-derived pigment neuromelanin, which is not found in such abundance in other species and has been associated with toxicity at higher levels. The oxidative stress created by their DA production system, despite that the SN does not use unusually high amounts of energy, explains why SNc DA neurons are sensitive to various genetic and environmental factors that create mitochondrial damage and thereby promote PD. Aging increases multiple of the risk factors for PD, and, to a large extent, PD is accelerated aging. To prevent PD neurodegeneration, possible approaches that are discussed here are (1) reducing cytoplasmic DA accumulation, (2) blocking cytoplasmic Ca2+ oscillations, and (3) providing bioenergetic support.

The cytokine-producing nucleotide-binding domain leucine-rich repeat and pyrin-containing receptor 3 (NLRP3) inflammasome is generally recognized to play a central role in the immune response to vaccination and NLRP3 activity is known to be increased by both aluminum adjuvants and by oxidative stress. Thus, the presence of oxidative stress may place individuals at higher risk for exaggerated or prolonged inflammatory responses and related side effects from vaccination. We here examine the relationship between oxidative stress and NLRP3 inflammasome activity, particularly in the context of aluminum-adjuvanted vaccines, and its implications for subpopulations of individuals with restricted antioxidant capacity.

The oxidative coupling of methane (OCM) to produce ethane and ethylene (C2 compounds) as platform chemicals involves complex chemistry with reactions both in the gas phase and on the catalyst surface, resulting in a distribution of products at the expense of C2 selectivity. This work uses experimental data from a variety of mixed metal oxides on supports at different reaction conditions (temperature, contact time, and reactant flow rates) to train a random forest regressor that predicts methane conversion and C2 selectivity (key performance indicators (KPIs)), and deploys it to locate optimal conditions that maximize C2 yield for a catalyst. Investigating the regressor interpretability via feature importance reveals that the choice of metals and support are crucial to C2 selectivity predictions, while the predictions of methane conversion are driven by the reaction conditions. The machine learning (ML) regressor is used as a surrogate to develop performance curves for each of the catalysts via a multi-objective optimization routine that seeks to maximize the KPIs in the decision space of reaction conditions, is seen to locate optimal conditions at which the maximum C2 yields for catalysts are predicted to be 15%, higher on average. Analyzing the catalysts in the space of their performance curves with respect to a popular OCM catalyst, Mn-Na2WO4/SiO2, reveals distinct patterns based on intrinsic properties of metals and supports. Further, the decision space with catalyst descriptors and reaction conditions is optimized for high C2 yields using the ML surrogate, in a static multi-objective optimization routine, and an adaptive Bayesian routine, where the latter was found to have a wider field focus in proposing catalyst formulations and conditions. Transition metal oxides on a variety of supports were proposed but not their lanthanide oxide counterparts.

Hemoglobin is one of the proteins that are more susceptible to S-glutathionylation and the levels of its modified form, glutathionyl hemoglobin, increase in several human pathological conditions. The scope of the present review is to provide knowledge about how hemoglobin is subjected to be S-glutathionylated and how this modification affects its functionality. The different diseases that showed increased levels of glutathionyl hemoglobin and the methods used for its quantification in clinical investigations will be also outlined. Since there is a growing need for precise and reliable methods of markers of oxidative stress in human blood, this review highlights how glutathionyl hemoglobin is more and more emerging as a good indicator of severe oxidative stress but also as a key pathogenic factor in several diseases.

Castor oil may be differentiated from other non-edible vegetable oils because of its main composition of hydroxylated fatty acids. Ricinoleic acid comprises 80–90% wt. of fatty acids in castor oil (Ricinus communis). In this study, the thermo-oxidative stability and tribological behavior of bio-based lubricant samples synthesized from castor oil using isoamyl alcohol were evaluated. Initially, the compositional and physicochemical properties of the obtained samples were assessed using 1H NMR, FTIR, and ASTM methods. Oxidative stability of the samples was evaluated using Rancimat method at 110 °C under air flow. The final biolubricant sample (BL2), obtained after esterification, epoxidation, and oxirane rings opening reactions, presented an oxidation stability time (OST) of 14.3 h. The thermal stability was also evaluated by thermogravimetry (TG) from the mass variations under inert and oxidative atmosphere. BL2 showed higher thermal stability compared to the other samples, demonstrating higher decomposition temperatures in both inert (339.04 °C) and oxidative (338.47 °C) atmospheres, for a mass loss of 50%. The tribological properties of the samples were evaluated using a four-ball tribometer configuration. The BL1 and BL2 samples exhibited lower friction coefficients than the mineral oil sample (MOS) by 21.5% and 43.1%, respectively. Regarding wear, the observed wear scar diameter (WSD) was also lower in BL1 and BL2 compared to MOS by 5.2% and 40.4%, respectively. The results of the tribological evaluation suggest that both samples obtained in this study have promising potential for applications in lubricating machines and mechanical systems.

Centella asiatica (Centella) is a traditional botanical medicine that shows promise in treating dementia based on behavioral alterations seen in animal models of aging and cognitive dysfunction. In order to determine if Centella could similarly improve cognitive function and reduce disease burden in multiple sclerosis (MS), we tested its effects in the neuroinflammatory experimental autoimmune encephalomyelitis (EAE) model of MS. In two independent experiments, C57BL/6J mice were treated following induction of EAE with either a standardized water extract of Centella (CAW) or placebo for 2 weeks. At the dosing schedule and concentrations tested, CAW did not improve behavioral performance, EAE motor disability, or degrees of demyelination. However, CAW-treated mice demonstrated increases in nuclear factor (erythroid-derived 2)-like 2 and other antioxidant response element genes, and increases in mitochondrial respiratory activity. Caw also decreased spinal cord inflammation. Our findings indicate that CAW can increase antioxidant gene expression and mitochondrial respiratory activity in mice with EAE, supporting investigation of the clinical effects of CAW in people with MS.

Margarines are W/O emulsions with minimal fat and are heat treated when used for baking. Lipid oxi-dation has been identified as the major deterioration process of margarines and addition of antioxidants is necessary. Consumers are increasingly demanding that chemical antioxidants in foods be replaced by natural preservatives. A multivariate statistical study gave us oxidative stability depending on the com-position of 20 different commercial margarines and an analysis of the principal components allowed us to classify and select eight of them. This study analyzes the antioxidant capacity of six different natural ground herbs (Curcuma longa, Illicium verum, Rosmarinus officinalis, Taraxacum officinale, Thymus piperella and Thymus vulgaris) on the oxidative stability of eight selected margarines. In order to evalu-ate the oxidative stability, we determine the induction period (IP) with Rancimat assays at 120 ºC with 1.5 hours of suppression. As results, Rosmarinus officinalis increases the IP value by 73.17% with respect to its basal values, Curcuma longa, Thymus vulgaris and Thymus piperella increases it between 17% and 26% and Taraxacum officinale together with Illicium verum reduces it between 19% and 34% respec-tively. A multiple linear regression model approach shows that IP has a positive correlation with SFA, PUFA,  acids, MUFA/PUFA ratio and antioxidant activity.

The channels from the superfamily of transient receptor potential (TRP) activated by reactive oxygen species (ROS) are defined as redox channels. Those with the best exposure of the cysteine residues and hence the most sensitive to oxidative stress are TRPC4, TRPC5, TRPV1, TRPV4, and TRPA1, while others, such as TRPM2 and TRPM7 are indirectly activated by ROS. Activation by ROS has different effects on the tumorigenic process: some TRP channels may, upon activation, stimulate proliferation, apoptosis, or migration of cancer cells, while others inhibit these processes, depending on the cancer type, tumoral microenvironment and finally on the methods used for evaluation. Therefore, the use of these polymodal proteins as therapeutic targets is still an unmet need, despite their draggability and modulation by simple and mostly unharmful compounds. In this review, we intend to create some cellular models of the interaction between oxidative stress, TRP channels, and inflammation. Although the crosstalk between the three actors is rather theoretical, we intended to gather the recently published data and proposed pathways of cancer inhibition using modulators of TRP proteins, hoping that the experimental data corroborated with clinical information may finally bring the results from the bench to the bedside.

Repeated exposure to environmental ozone causes a chronic state of oxidative stress. This state is present in chronic degenerative diseases and induces a loss of control of the inflammatory response. The dysfunction of redox system and failures in control the inflammatory responses are involved in a vicious circle that maintains and increases the degenerative process. Intestine also responds to secondary reactive species formed by exposure to ozone doses, generating noxious stimuli that increase degenerative damage. This review aims to elucidate how environmental pollution, mainly by ozone, induces a state of chronic oxidative stress with the loss of regulation of the inflammatory response, both in the intestine and in the brain, where the functionality of both structures is altered and plays a determining role in some neurodegenerative and chronic degenerative diseases. For this purpose, we searched for information on sites like the Cochrane Library Database, PubMed, Scopus, and Medscape. Reviewing the data published, we can conclude that environmental pollutants are a severe health problem. Ozone pollution has different pathways of action, both molecular and systemic, and participates in neurodegenerative diseases such as Parkinson's and Alzheimer's disease as well in bowel diseases as Inflammatory Bowel Disease, Crohn's Disease and Irritable Bowel Syndrome.

Pneumonia is a severe lower respiratory tract infection that is a common complication and a major cause of mortality of the vitamin C-deficiency disease scurvy. This suggests an important link between vitamin C status and lower respiratory tract infections. Due to the paucity of information on the vitamin C status of patients with pneumonia, we assessed the vitamin C status of 50 patients with community-acquired pneumonia and compared these with 50 healthy community controls. The pneumonia cohort comprised 44 patients recruited through the Acute Medical Assessment Unit (AMAU) and 6 patients recruited through the intensive care unit (ICU); mean age 68 ± 17 years, 54% male. Clinical, microbiological and haematological parameters were recorded. Blood samples were tested for vitamin C status using HPLC with electrochemical detection and protein carbonyl concentrations, a marker of oxidative stress, using ELISA. Patients with pneumonia had depleted vitamin C status compared with healthy controls (23 ± 14 µmol/L vs 56 ± 24 µmol/L, P <0.001). The more severe patients in the ICU had significantly lower vitamin C status than those recruited through AMAU (11 ± 3 µmol/L vs 24 ± 14 µmol/L, P = 0.02). The total pneumonia cohort comprised 62% with hypovitaminosis C and 22% with deficiency, compared with only 8% hypovitaminosis C and no cases of deficiency in the healthy controls. The pneumonia cohort also exhibited significantly elevated protein carbonyl concentrations compared with the healthy controls (P < 0.001), indicating enhanced oxidative stress in the patients. We were able to collect subsequent samples form 28% of the cohort (mean 2.7 ± 1.7 days; range 1-7 days). These showed no significant differences in vitamin C status or protein carbonyl concentrations compared with baseline values (P = 0.6). Overall, the depleted vitamin C status and elevated oxidative stress observed in the patients with pneumonia indicates an enhanced requirement for the vitamin during their illness. Due to the important roles that vitamin C plays in the immune system, low vitamin C status is possibly both a cause and a consequence of the disease. Therefore, these patients would likely benefit from additional vitamin C supplementation to restore their blood and tissue levels to optimal. This may decrease oxidative stress and aid in their recovery.

Terpenoids are toxic compounds produced by plants as a defense strategy against insect herbivores. We tested the effect of Origanum vulgare terpenoids on the generalist herbivore Spodoptera littoralis and the response of the plant to herbivory. Terpenoids were analyzed by GC-FID and GC-MS and quantitative gene expression (qPCR) was evaluated on selected plant genes involved in both terpene biosynthesis. The insect detoxification response to terpenes was evaluated by monitoring antioxidant enzymes activity and expression of insect genes involved in terpene detoxification. O. vulgare terpenoid biosynthesis and gene expression was modulated by S. littoralis feeding. The herbivore-induced increased level of terpenoids (particularly carvacrol and p-cymene) interacted with the herbivore by decreasing larval survival and growth rate. The assimilation by S. littoralis of more than 50% of ingested terpenes correlated with the possible toxic effects of O. vulgare terpenoids. In choice test experiments, carvacrol and γ-terpinene mediated the larval feeding preferences, wherease the prolonged feeding on O. vulgare terpenoids (particularly on γ-terpinene) exerted relevant antinutritional effects on larvae. S. littoralis was found to react to O. vulgare terpenoids by increasing its antioxidant enzymes activities and gene expression, although this was not sufficient to sustain the toxicity of O. vulgare terpenoids.

Optic nerve disorders encompass a wide spectrum of conditions characterized by the loss of retinal ganglion cells (RGCs) and subsequent degeneration of the optic nerve. The etiology of these disorders can vary significantly, but emerging research highlights the crucial role of oxidative stress, an imbalance in the redox status characterized by an excess of reactive oxygen species (ROS), in driving cell death through apoptosis, autophagy, and inflammation. This review provides an overview of ROS-related processes underlying four extensively studied optic nerve diseases: glaucoma, Leber's hereditary optic neuropathy (LHON), anterior ischemic optic neuropathy (AION), and optic neuritis (ON). Furthermore, we present preclinical findings on antioxidants, with the objective of evaluating the potential therapeutic benefits of targeting oxidative stress in the treatment of optic neuropathies.

This study investigated the neuroprotective effects of methyl 3,4-dihydroxybenzoate (MDHB) against t-butylhydroperoxide(TBHP) induced oxidative damage in SH-SY5Y (human neuroblastoma cells) and the underlying mechanisms. SH-SY5Y were cultured in DMEM+10% FBS for 24 hours and pretreated with different concentrations of MDHB or N-acetyl-L-cysteine (NAC) for 4 hours prior to the addition of 40 μM TBHP for 24 hours. Cell viability was analyzed using the methyl thiazolyl tetrazolium (MTT) and lactate dehydrogenase (LDH) assays. An annexin V-FITC assay was used to detect cell apoptosis rate. The 2',7'-dichlorofluorescin diacetate (DCFH-DA) assay was used to determine intracellular ROS levels. The activities of antioxidative enzymes (GSH-Px and SOD) were measured using commercially available kits. The oxidative DNA damage marker 8-OHdG was detected using ELISA. Western blotting was used to determine the expression of Bcl-2, Bax, caspase 3, p-Akt and Akt proteins in treated SH-SY5Y cells. Our results showed that MDHB is an effective neuroprotective compound that can mitigate oxidative stress and inhibit apoptosis in SH-SY5Y cells

In the present study we tested the effect of small molecular weight redox molecules on collagen-induced platelet aggregation. We used N-acetylcysteine amide (AD4), the amide form of N-acetylcysteine (NAC), a thiol antioxidant with improved lipophilicity and bio-availability compared to NAC, and the thioredoxin mimetics (TXM) peptides, TXM-CB3, TXM-CB13, and TXM-CB30. All compounds significantly inhibited platelet aggregation induced by collagen, with TXM-peptides and AD4 being more effective than NAC. The levels of TxB2 and 12-HETE, the main metabolites derived from the cyclooxygenase and lipoxygenase pathways following platelet activation, were significantly reduced in the presence of AD4, TXM-peptides, or NAC, when tested at the highest concentration (0.6 mM). The effect of AD4, TXM-peptides, and NAC was tested also on the clotting time (CT) of whole blood. TXM-CB3 and TXM-CB30 showed the highest increase of CT. Furthermore, two representative compounds, TXM-CB3, and NAC, showed an increase in the an-ti-oxidant free sulfhydryl groups of plasma detected by Ellman’s method, suggesting a contribution of plasma factors to the antiaggregating effects. Our results suggest that these small molecular weight redox peptides might become useful for the prevention and/or treatment of oxidative stress conditions associated with platelet activation.

Background: There is now evidence that schizophrenia and deficit schizophrenia are neuro-immune conditions and that oxidative stress toxicity (OSTOX) may play a pathophysiological role. Aims of the study: To compare OSTOX biomarkers and antioxidant (ANTIOX) defenses in deficit versus non-deficit schizophrenia. Methods: We examined lipid hydroperoxides (LOOH), malondialdehyde (MDA), advanced oxidation protein products (AOPP), sulfhydryl (-SH) groups, paraoxonase 1 (PON1) activity and PON1 Q192R genotypes, total radical-trapping antioxidant parameter (TRAP) as well as immune biomarkers in patients with deficit (n=40) and non-deficit (n=40) schizophrenia and healthy controls (n=40). Results: Deficit schizophrenia is characterized by significantly increased levels of AOPP and lowered -SH, and PON1 activity, while no changes in the OSTOX/ANTIOX biomarkers were found in non-deficit schizophrenia. An increased OSTOX/ANTIOX ratio was significantly associated with deficit versus non-deficit schizophrenia (Odds ratio=3.15, p<0.001). Partial least squares analysis showed that 47.6% of the variance in a latent vector extracted from psychosis, excitation, hostility, mannerism, negative symptoms, psychomotor retardation, formal thought disorders, and neurocognitive test scores was explained by LOOH+AOPP, PON1 genotype + activity, CCL11, tumor necrosis factor (TNF)-α, IgA responses to neurotoxic tryptophan catabolites (TRYCATs), whereas -SH groups and IgM responses to MDA showed indirect effects mediated by OSTOX and neuro-immune biomarkers. Discussion: Our findings indicate that with increasing overall severity of schizophrenia, neuro-immune and neuro-oxidative (especially protein oxidation indicating chlorinative stress) toxicities become more prominent and together with lowered antioxidant defenses and impairments in innate immunity-associated resilience against neurotoxic processes shape a distinct nosological entity, namely deficit schizophrenia.

Plants and its corresponding botanical preparations have been used for centuries due to their remarkable potentialities in both treatment and prevention of numerous affections. Hundreds of biologically active constituents are present in each whole plant matrice, working in synergism and conferring both its own protection against invaders and even providing promissory bioactive effects for human beings. The worldwide population has devoted increasing attention and preference by medicinal plants use for health promotion and disease prevention, and more recently for oxidative-stress related disorders protection. Indeed, oxidative stress-related disorders, like cardiovascular and (neuro) degenerative disorders, and even cancer have raised exponentially. Although oxidative stress is in itself intrinsic to our own metabolism, allarming sources of free radicals are daily affecting us. In fact, plant-derived bioactives present a broad spectrum of biological effects, and its antioxidant, anti-inflammatory and more recently anti-aging effects have been considered a hot topic among the medical and scientific community. Nonetheless, and although its numerous biological effects, it should not also be forgotten that some bioactive molecules are prone to oxidation and can even exert pro-oxidant effects. In this sense, the objective of the present review is to provide a detailed overview on plant-derived bioactives in oxidative stress-related disorders. Specifically, the role of phytochemicals as antioxidants and pro-oxidant agents is carefully addressed, as is its therapeutic relevance in disease prevention. Finally, an eye-opening look in overall evidence in humans is also ensured.

Non-Alcoholic Fatty Liver Disease (NAFLD) is a term that covers a range of hepatic disorders involving fat deposits in the liver. NAFLD begins with simple steatosis and progresses into non-alcoholic steatohepatitis (NASH) characterised by inflammation, fibrosis, apoptosis, oxidative stress, lipid peroxidation, mitochondrial dysfunction and release of adipokines and pro-inflammatory cytokines. Oxidative stress and antioxidants are known to play a vital role in the pathogenesis and severity of NAFLD/NASH. A number of oxidative stress and antioxidant markers are employed in the assessment of the pathological state and progression of the disease. In this article, we review several biomarkers of oxidative stress and antioxidants that have been measured at clinical and experimental levels. The levels/ activity in various models reviewed are also included. Also included is a comprehensive description of oxidative stress, sources and contribution to the pathogenesis of NAFLD/NASH

Atherosclerotic cardiovascular disease, a leading cause of morbidity and mortality worldwide, is a chronic inflammatory disease, linked to a state oxidative stress, with several well-identified culprits, of which low-density-lipoprotein cholesterol (LDL-C) and lipoprotein(a). No specific treatment is currently available to lower lipoprotein(a). It is, therefore, of paramount importance to identify nutritional factors that could lower lipoprotein(a). Growing evidence shows that although reducing saturated fatty acid (SFA) intake decreases LDL-C, it could increase lipoprotein(a). Optimal dietary recommendations may therefore differ depending on an in-dividual’s baseline lipoprotein(a) and LDL-C levels. Assessing the diet-induced true LDL-C response and net balance of these two atherogenic entities is difficult because LDL-C measurement is confounded by lipoprotein(a) cholesterol content. We have estimated, for the first time, the net atherogenic result of diet-induced variations of both LDL-C and lipoprotein(a), thanks to our new concept of LDLapoB risk equivalent=apoB+lp(a)x5 (in nmol/L). This is illustrated, via the rare case of a physician with very high lipoprotein(a) and hypobetalipoproteinemia. She experiences twice a considerable lipoprotein(a) increase (+32%, + 28mg/dL, + 67nmol/L) and higher LDLapoB risk equivalent (138mg/dL versus 123mg/dL) on a mediterranean diet, low in SFA. A reasonable SFA intake, despite causing marginal LDL-C increase, may be advisable in patients with high lipoprotein(a) who need personalized dietary recommendations.

Neuroinflammation and brain oxidative stress are recognized as significant contributors to hypertension including salt sensitive hypertension. Extracellular vesicles (EVs) play an essential role in intercellular communication in various situations, including physiological and pathological ones. Based on this evidence, we hypothesized that EVs derived from the brains of hypertensive rats with salt sensitivity could trigger neuroinflammation and oxidative stress during hypertension development. To test this hypothesis, we compared the impact of EVs isolated from the brains of hypertensive Dahl Salt Sensitive rats (DSS) and normotensive Sprague Dawley (SD) rats on inflammatory factors and mitochondrial reactive oxygen species (mtROS) production in primary neuronal cultures and brain cardiovascular relevant regions, including the hypothalamic paraventricular nucleus (PVN) and lamina terminalis (LT). We found that brain-derived DSS-EVs significantly increased mRNA levels of proinflammatory cytokines (PICs) and chemokines, including TNFα, IL1β, CCL2, CCL5, and CCL12, as well as the transcriptional factor NF-κB in neuronal cultures. DSS-EVs also induced oxidative stress in neuronal cultures, as evidenced by elevated NADPH oxidase subunit CYBA coding gene mRNA levels and persistent mtROS elevation. When DSS-EVs were injected into the brains of normal SD rats, mRNA levels of PICs, chemokines, and the chronic neuronal activity marker FOSL1 were significantly increased in the PVN and LT. Furthermore, DSS-EVs caused mtROS elevation in brain PVN and LT, particularly in neurons. Our study reveals a novel role for brain-derived EVs from hypertensive rats in triggering neuroinflammation, upregulating chemokine expression, and inducing excessive ROS production. These findings provide insight into the complex interactions between EVs and hypertension-associated processes, offering potential therapeutic targets for hypertension-linked neurological complications.

Atrial fibrillation (AF) is a cardiac arrhythmia caused by electrophysiological anomalies in the atrial tissue, tissue degradation, structural abnormalities, and comorbidities. A direct relation exists between AF and altered mitochondrial activity resulting from membrane potential loss, contractile dysfunction, or decreased ATP levels. This review aimed to elucidate the role of mitochondrial oxidative mechanisms in AF pathophysiology, the impact of mitochondrial oxidative stress on AF initiation and perpetuation, and current therapies. This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Extension for Scoping Reviews. PubMed, Excerpta Medica Database, and Scopus were explored until June 2023 using "MESH terms." Bibliographic references from relevant papers were also included. Oxidative stress is an imbalance that causes cellular damage from excessive oxidation, resulting in conditions such as AF. An imbalance in reactive oxygen species production and elimination can cause mitochondrial damage, cellular apoptosis, and cardiovascular diseases. Oxidative stress and inflammation are intrinsically linked, and inflammatory pathways are highly correlated with the occurrence of AF. AF is an intricate cardiac condition that requires innovative therapeutic approaches. The involvement of mitochondrial oxidative stress in the pathophysiology of AF introduces novel strategies for clinical treatment.

Abstract: Down Syndrome (DS) is a common genetic disorder characterized by an extra copy of chromosome 21, leading to dysregulation of various metabolic pathways. Oxidative stress in DS is associated with neurodevelopmental defects, neuronal dysfunction, and the onset of dementia re-sembling Alzheimer's disease. Additionally, chronic oxidative stress contributes to cardiovascular diseases and certain cancers prevalent in DS individuals. This study investigates the impact of ageing on oxidative stress and liver fibrosis using a DS murine model (Ts2Cje mice). The liver in DS mice shows increased oxidative stress and impaired antioxidant defenses, as evidenced by reduced glutathione levels and increased lipid peroxidation. Furthermore, DS liver exhibits an altered in-flammatory response as measured by the expression of cytokines and heat shock proteins. DS liver also displays dysregulated lipid metabolism, indicated by altered expression of peroxisome prolif-erator-activated receptors and fatty acid transport proteins. Consistently, these changes might contribute to non-alcoholic fatty liver disease development, a condition characterized by liver fat accumulation. Finally, histological analysis of DS liver reveals increased fibrosis and steatosis, in-dicative of potential progression to liver cirrhosis. This finding highlights the increased risk of liver pathologies in DS individuals, particularly when combined with the higher prevalence of obesity and metabolic dysfunctions in DS patients. These results shed light on the liver's role in DS-associated pathologies and suggest potential therapeutic strategies targeting oxidative stress and lipid metabolism to prevent or mitigate liver-related complications in DS individuals.

Previously, we reported that MTH1 inhibitors TH588 and TH1579 selectively induce oxidative damage and kill Ras expressing or transforming cancer cells, as compared to non-transforming immortalized or primary cells. While this explains the impressive anti-cancer properties of the compounds, the molecular mechanism remains elusive. Oncogenes induce replication stress, re-sulting in under replicated DNA and replication continuing into mitosis, where TH588 and TH1579 treatment cause toxicity and incorporation of oxidative damage. Hence, we hypothesized that oncogene-induced replication stress explains the cancer selectivity. To test this, we overex-pressed c-Myc in human epithelial kidney cells (HA1EB), resulting in increased proliferation, polyploidy and replication stress. TH588 and TH1579 selectively kill c-Myc overexpressing clones, enforcing the cancer cell selective killing of these compounds. Moreover, the toxicity of TH588 and TH1579 in c-Myc overexpressing cells is rescued by transcription, proteasome or CDK1 inhibitors, but interestingly not by nucleoside supplementation. This suggest that cancer selectivity is unrelated oncogene-induced replication stress. We conclude that the molecular toxi-cological mechanisms how TH588 and TH1579 kill c-Myc overexpressing cells have several com-ponents and involves MTH1-independent proteosomal degradation of c-Myc itself, c-Myc driven transcription and CDK activation, and is likely unrelated to oncogene-induced replication stress.

Glaucoma is one of the most common causes of irreversible vision loss worldwide. It is an insidious disease with a multifactorial pathogenesis. Despite progress in treatment methods, prevention and lifestyle modifications may be useful in slowing the progression of this disease. This systematic review aimed to evaluate the influence of diet, oxidative stress, and disturbances in blood serum levels of nutrients on the incidence and severity of glaucoma based on scientific reports on the role of nutrition in the pathogenesis and course of glaucoma. This paper presents an analysis of the above issues; however, further research is required to develop this topic. Future clinical trials are needed to assess the influence of nutrition and to develop nutritional management strategies for patients with glaucoma.

The prevalence of nonalcoholic fatty liver disease (NAFLD) has been rapidly increasing worldwide. A choline-deficient L-amino acid-defined high fat diet (CDHFD) has been used to create a mouse model of nonalcoholic steatohepatitis (NASH). There are some reports about the effects on mice of being fed CDAHFD for a long time, 1 to 3 months. However, the effect of this diet over a short period has been unknown. Therefore, we examined the effect of one week of feeding CDAHFD on the mouse liver. Feeding this diet for only one week induced lipid droplet deposition in the liver with increasing activity of liver-derived enzymes in the plasma. On the other hand, it did not induce fibrosis and cirrhosis. Additionally, it was demonstrated that mitochondrial respiration is significantly impaired with severe oxidative stress in the liver by CDAHFD, associated with a decreasing mitochondrial DNA copy number and complexes-proteins. In the gene expression analysis of the liver, inflammatory and oxidative stress markers were significantly increased by CDAHFD. These results demonstrated that one week of feeding CDAHFD to mice induces steatohepatitis with mitochondrial dysfunction and severe oxidative stress, without fibrosis, which can partially mimic the early stage of the NASH in humans.

During the last decade, essential polyunsaturated fatty acids (PUFAs) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) derived from marine sources have been investigated as nonpharmacological dietary supplements to improve different pathological conditions, as well as aging. The aim of this study was to determine the effects of dietary n-3 PUFA monoacylglycerides (MAG, both EPA and DHA) on the mitochondrial metabolism and oxidative stress of a short-lifespan model, Drosophila melanogaster, sampled at five different ages. Our results showed that diets supplemented with MAG-EPA and MAG-DHA increased median lifespan by 14.6% and decreased mitochondrial proton leak resulting in an increase of mitochondrial coupling. The flies fed on MAG-EPA also had higher electron transport system capacity and mitochondrial oxidative capacities. Moreover, both n-3 PUFAs delayed the occurrence of lipid peroxidation, but only flies fed the MAG-EPA diet showed maintenance of superoxide dismutase activity during aging. Our study therefore highlights the potential of n-3 PUFA monoacylglycerides as nutraceutical compounds to delay the onset of senescence by acting directly or indirectly on the mitochondrial metabolism, and suggests that Drosophila could be a relevant model for the study of the fundamental mechanisms linking the effects of n-3 PUFAs to aging.

Accumulating evidence suggests that metformin, used as an antidiabetic drug, possesses anticancer properties. Metformin reduced the incidence and growth of experimental tumors in vivo. In a randomized clinical trial among nondiabetic patients, metformin treatment significantly decreased the number of aberrant crypt foci compared to the untreated group with a follow-up of 1 month. In our study, HT29 cells were treated with graded concentrations of metformin, 10 mM/25 mM/50 mM, for 24/48 hours. We performed immunofluorescence experiments by means of confocal microscopy and Western blot analysis to evaluate a panel of factors involved in apoptotic/autophagic processes and oxidative stress response. Moreover, HT29 cells treated with metformin were analyzed by flow cytometry assay to detect the cell apoptosis rate. The results demonstrate that metformin exerts growth inhibitory effects on cultured HT29 cells by increasing both apoptosis and autophagy; moreover, it affects the survival of cultured cells inhibiting the transcriptional activation of nuclear factor E2–related factor 2 (NRF-2) and nuclear factor–kappa B (NF-κB). The effects of metformin on HT29 cells were dose- and time-dependent. These results are very intriguing, since metformin is emerging as a multifaceted drug: it has a good safety profile and is associated with low cost, and it might be a promising candidate for the prevention or treatment of colorectal cancer.

Studies have shown that aerosols generated from flavored e-cigarettes contain Reactive Oxygen Species (ROS), promoting oxidative stress-induced damage within pulmonary cells. Our lab investigated the ROS content of e-cigarette vapor generated from disposable vape bars, a product exempt from the Federal Drug Enforcement Agency’s (FDA) 2020 flavor ban. Specifically, we analyzed vape bars belonging to multiple flavor categories (Tobacco, Minty Fruit, Fruity, Minty/Menthol, Desserts, and Drinks), manufactured by various vendors and of various nicotine concentrations (0-6.8%). Aerosols from these flavored vape bars were generated by a single puff aerosol generator and individually bubbled through a fluorogenic solution to detect and semi-quantify ROS in H2O2 equivalents generated by the vape bars. We compared and contrasted the ROS levels generated by each flavor as an indirect determinant of oxidative stress potential by these disposable vape bars. Our results showed that ROS concentration (μM) of aerosols produced from the vape bars varied significantly between different flavors and a function of nicotine concentration. Likewise, our results suggest that flavoring chemicals and nicotine concentration play a role in alerting ROS production in e-cigarette aerosols. Our study provides insight into the differential health effects of flavored disposable vape bars and the need for their regulation.

Pirin is an oxidative stress (OS) sensor belonging to the functionally diverse cupin superfamily of proteins. Pirin is a suggested quercetinase and transcriptional activator of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway. Its biological role in cancer development remains as a novel area of study. This review shows accumulating evidence on the contribution of Pirin in epithelial cancers, signaling pathways involved, and as a suggested therapeutic target. Finally, we propose a model in which Pirin is upregulated by physical, chemical or biological factors involved in OS and cancer development.

Chronic high glucose (HG) exposure increases methylglyoxal (MG)-derived AGEs and is involved in the onset of pathological conditions, such as diabetes, atherosclerosis and chronic‐degenerative diseases. Under physiologic condition the harmful effects of MG are contrasted by glyoxalase system that is involved in the detoxification of Reactive Carbonyl Species (RCS) and maintain the homeostasis of the redox environment of the cell. Polyphenols are the most abundant antioxidants in the diet and present various health benefits. The study aimed at investigating the role of polyphenols extracted from an apple high in polyphenols (Calville White Winter), on glyco-oxidative stress induced by chronic HG-exposure. Intestinal Caco-2 cells were treated in physiological glucose condition (25mM) as a control and in HG condition (50mM) with or without apple extract for one week. Our data demonstrated that HG-treatment triggers glyco-oxidation stress with a significantly increase in ROS, lipid peroxidation, AGEs and Glyoxalase I (GlxI) activity with a significant decrease in total antioxidant intracellular defense. Treatment with polyphenols under HG condition restores to the control levels GlxI activity, decreases Glyoxalase II (GlxII) in relation to the control and induces a drop of glyco-oxidative damage. This paper seeks to highlight the roles of polyphenols in glyco-oxidative stress.

This paper focused on the oxidative leaching process of vanadium from vanadium-chromium reducing residue in alkaline medium with MnO₂. The effect of experimental parameters including reaction time, reaction temperature, dosage of MnO₂, dosage of NaOH, and liquid-to-solid ratio on the leaching efficiency of vanadium had been studied. The results indicated that MnO₂ was an efficient oxidant for leaching out of vanadium. The leaching efficiency of vanadium was up to 97.25% under optimal reaction conditions: reaction temperature of 90 ℃, reaction time of 60 min, dosage of MnO₂ at 50 wt.%, concentration of NaOH at 30 wt.% and liquid-to-solid at 5:1 mL/g.

The present study aimed to analyze novel mechanisms underlying Nrf2-mediated anti-apoptosis in periodontal ligament stem cells (PDLSCs) in the periodontitis oxidative microenvironment. We created an oxidative stress model with H2O2-treated PDLSCs. Herein, we used real-time PCR, western blotting, TUNEL staining, fluorogenic assay and transfer genetics to confirm the degree of oxidative stress and apoptosis as well as the Nrf2 function. Surprisingly, we demonstrated that with up-regulated ROS and MDA levels, the effect of oxidative stress was obvious under H2O2 treatment. Anti-oxidative molecules were changed after the H2O2 exposure, whereby the anti-oxidative signaling of Nrf2 was activated with the increase of its downstream effectors, HO-1, NQO1 and γ-GCS. Additionally, the apoptosis levels gradually increased with oxidative stress and changes in the caspase-9, caspase-3, Bax and c-Fos levels, but not with caspase-8 and down-regulated Bcl-2. The enhanced antioxidant effect could not resist the occurrence of apoptosis. Furthermore, Nrf2 overexpression effectively improved the anti-oxidative levels and increased cell proliferation. At the same time, overexpression effectively restrained TUNEL staining and decreased the molecular levels of caspase-9, caspase-3, et al, but not that of caspase-8. By contrast, silencing the expression Nrf2 levels had the opposite effect. Collectively, Nrf2 alleviates PDLSCs via its effects on anti-oxidative and anti-intrinsic apoptosis by the activation of anti-oxidative enzymes.

(1) Background: The severity of malaria is associated with low bioavailability of antioxidants and high concentration of free radicals that induce oxidative damage in cerebral and pulmonary microcirculation. This can be prevented by the action of consumable antioxidants present in foods. Therefore, we investigated the protective role of lycopene (LYC) on the oxidative changes induced by Plasmodium berghei (Pb); (2) Methods: Mice were infected by intraperitoneal injection of 106 parasitized red blood cells and treated via gavage with LYC (3.11 mg/kg bw/day) or NAC (62 mg/kg bw/day). They were then evaluated for 1, 4, 8 or 12 days after infection. Levels of thiobarbituric acid reactive substances (TBARS), antioxidant capacity by inhibition of ABTS radicals (AC-ABTS) and DPPH (AC-DPPH), uric acid (UA), and nitric oxide (NO) were measured in brain and lung tissues; (3) Results: The infection caused oxidative stress confirmed by increased levels of TBARS, AC-ABTS, AC-DPPH, UA, and NO in the tissues leading to the death of the animals. LYC prevented the increase in TBARS, AU, and NO levels compared to Pb (p&lt; 0.0001) and NAC+Pb groups (p&lt;0.0001), reaching values similar to those of Sham animals; (4) Conclusions: These results are striking evidence of the beneficial effect of lycopene supplementation on oxidative stress in experimental malaria in vivo and emphasize the importance of antioxidant supplementation in the treatment of the disease.

Chronic obstructive pulmonary disease (COPD) is a respiratory disease associated with airways inflammation and lung parenchyma fibrosis. The primary goals of COPD treatment are to re-duce symptoms and risk of exacerbations, therefore pulmonary rehabilitation is considered the key component of managing COPD patients. Oxidative airway damage, inflammation and re-duction of endogenous antioxidant enzymes are known to play a crucial role in the pathogenesis of COPD. Natural antioxidants have also recently been considered as they play an important role in metabolism, DNA repair and fighting the effects of oxidative stress. In this paper we evaluated the response of 105 elderly COPD patients to pulmonary rehabilitation (PR), based on high or low vegetable consumption, by analyzing clinical parameters and biological measure-ments at baseline and after completion of the three weeks PR. We found that high vegetable in-take in normal diet, without any specific intervention, can increase the probability to success-fully respond to rehabilitation (65.4% of responders ate vegetables daily vs. 40.0% of Non-Responders, p=0.033). Three weeks of pulmonary rehabilitation are probably too short to reveal a reduction of the oxidative stress and DNA damage, but are enough to show an im-provement in the patient's inflammatory state.

Today, air pollution is the greatest threat to organismal healthspan. The environment of our planet earth, the habitat of over eight billion humans and estimated twenty billion billions other animals, is contaminated with a wide variety of pollutants. Unfortunately, humans, out of billions and billions of living organisms on earth, are solely responsible for polluting the environment through emitting pollutants like particulate matter from industry, fuel engine vehicles, biomass combustion, toxic fumes from blasting, and wildfire. In the modern world, human-caused air pollutants induce massive oxidative stress and inflammation, the major contributors in initiation and progression of many diseases including pulmonary, cardiovascular, renal, hepatic, reproductive, neurological, mental, and accelerated biological aging. The provocative question is the following: how can we solve this human-created problem? As it is not realistic to clean the environment at once from human-caused pollution, initiatives have been undertaken to develop novel therapeutic approaches to control air-pollutant-induced oxidative stress and inflammation to protect humans from pollution-induced devastating diseases. In this article, I discuss the key findings of numerous recent preclinical studies documenting first, the role of air pollutant PM2.5 in augmentation of inflammation, oxidative stress, and associated diseases; and second, the efficacies of different natural and synthetic compounds in amelioration of PM2.5-induced oxidative stress, inflammation, pyroptosis, and associated pathologies.

Colistin is used in treatment against gram-negative bacteria. It causes toxic effects due to oxidative stress in a dose-dependent manner. Naringin is a flavonoid with strong antioxidant properties found naturally in many plants, especially citrus fruits. This study aimed to determine the protective effects of NRG in CLS-induced sciatic nerve injury. Thirty-five male Spraque rats were randomly divided into five groups: control, NRG, CLS, CLS+NRG50, and CLS+NRG100. CLS was administered orally at a 15mg/kg for seven days. NRG was administered orally at 50 or 100 mg/kg for seven days. CLS caused toxic damage in sciatic nerve tissue by increasing MDA and decreasing antioxidant capacity (SOD, CAT, GPx, and GSH); increasing NF-κB, TNF-α, nNOS release; increasing apoptotic factor (Caspase-3); decreasing HO-1 and nCAM; and inducing 8-OHdG, MAPK and GFAP. NRG, on the other hand, reversed all these changes in sciatic nerve tissue and reduced CLS-induced oxidative stress damage, inflammatory damage and apoptotic damage. These effects were more effective at the 100mg/kg dose of NRG than at the 50mg/kg dose. In sciatic nerve tissue, CLS-induced sciatic nerve toxicity with increased oxidative stress, inflammation, and apoptotic damage. NRG showed a protective effect against CLS-induced sciatic nerve toxicity.

Imidazo[1,2-a]pyridines have been studied regarding drug development. The objective of this work was to evaluate the antileukemic capacity of imidazo[1,2-a]pyridine derivatives by screening its ability as a pro-oxidant. Imidazo[1,2-a]pyridine derivatives were synthesized and oral bioavailability and toxicity were analyzed in silico. Redox screening was performed on human Kasumi, KG-1, K562 and Jurkat leukemia cells. The imidazo[1,2-a]pyridine derivative and the most responsive leukemic cell were selected for cytotoxicity, cell proliferation, cell senescence and oxidative stress assays. The predictive toxicity analysis showed a possible effect on the reproductive system, but without mutagenic, carcinogenic or irritability effects. MRK-107 against K562 cells was the compound that showed the best redox profile. MRK-107 did not induce cell death in K562 and monocyte cells. However, this compound was able to decrease cell proliferation and increase cell senescence after 48 and 72 hours. Furthermore, MRK-107 induced oxidative stress in K562 cells after 72h, increasing lipid peroxidation and decreasing reduced glutathione (GSH) contents. This study demonstrated that MRK-107-induced senescence with the involvement of oxidative stress as a possible mechanism of action, addressing this compound as a potential antitumor drug against chronic myeloid leukemia.

Microglia activation causes neuroinflammation, which is a hallmark of neurodegenerative disorders, brain injury, and aging. Ladostigil, a bifunctional reagent with antioxidant and anti-inflammatory properties, reduced microglial activation and enhanced brain functioning in elderly rats. In this study, we studied SH-SY5Y, a human neuroblastoma cell line, and tested viability in the presence of hydrogen peroxide and Sin1 (3-morpholinosydnonimine), which generates reactive oxygen and nitrogen species (ROS/RNS). Both stressors caused significant apoptosis and necrotic cell death that was attenuated by ladostigil. Our results from RNA-seq experiments show that long non-coding RNAs (lncRNAs) account for 30% of all transcripts in SH-SY5Y cells treated with Sin1 for 24 hours. Altogether, we identify 94 differently expressed lncRNAs in the presence of Sin1, including MALAT1, a highly expressed lncRNA with anti-inflammatory and anti-apoptotic functions. Additional activities of Sin-1 upregulated lncRNAs include redox homeostasis (e.g., MIAT, GABPB1-AS1), energy metabolism (HAND2-AS1), and neurodegeneration (e.g., MIAT, GABPB1-AS1, NEAT1). Four lncRNAs implicated as enhancers were significantly upregulated in cells exposed to Sin1 and ladostigil. Finally, we show that H2O2 and Sin1 increased the expression of DJ-1, a redox sensor and modulator of Nrf2 (nuclear factor erythroid 2–related factor 2). Nrf2 (NFE2L2 gene) is a major transcription factor regulating antioxidant genes. In the presence of ladostigil, DJ-1 expression is restored to its baseline. The mechanisms governing SH-SY5Y cell survival and homeostasis are highlighted by the beneficial role of ladostigil in the crosstalk involving Nrf2, antioxidant transcription factor DJ-1, and lncRNAs. Stress-dependent induction of lncRNAs represents an underappreciated regulatory level that contributes to cellular homeostasis and the capacity of SH-SY5Y to cope with oxidative stress.

Neurological disorders, such as amyotrophic lateral sclerosis, Parkinson’s disease, and Alzheimer’s disease, are commonly associated with persistent neuro-inflammation, and there is an urgent need to discover new therapeutic agents that may target the various pathways involved in neurodegeneration. In this study, we investigated the therapeutic potential of folecitin, a flavonoid isolated from Hypericum oblongifolium, against lipopolysaccharide (LPS)-induced oxidative stress associated with neurodegeneration, amyloidogenic Aβ production pathway, and memory dysfunction in mice. LPS was administered i.p. at 250 µg/kg/day for 3 weeks, followed by the administration of folecitin at a dose of 30 mg/kg/day for the last two weeks. A Western blot technique was used to assess the expression of different proteins involved in oxidative stress, neurodegeneration, and neuronal synapse. Results indicated that folecitin significantly reduced LPS-induced apoptotic neurodegeneration, including the expression of BAX, Caspase-3, and PARP-1 proteins, inhibited BACE1, and the amyloidogenic Aβ production pathway. Folecitin improved both pre- and post-neuronal synapse, as well as memory dysfunction. Furthermore, folecitin significantly activated endogenous antioxidant proteins such as Nrf-2 and HO-1 via stimulating the phosphorylation of Akt proteins. These findings suggest that folecitin may be a suitable lead to design new drugs for neurotoxin-triggered neurodegenerative disorders.

The immune system is a dynamic network of cells and cytokines are the major mediators of immune responses which combat pathogens. Based on the cytokine production, effector T cells differentiate into subsets known as Th1, Th2, Th17 or Treg (T regulatory). This system serves as a barrier to intracellular pathogens, bacterial infections and stimulates the production of reactive oxygen species (ROS), reactive nitrogen intermediates (RNI) and nitric oxide (NO), which diffuses across membranes and engulfs intracellular pathogens. Oxidative stress occurs when ROS, reactive nitrogen species (RNS) production and antioxidant defences become imbalanced. Oxidative stress generated by infected cells produces a substantial amount of free radicals which enables killing of intracellular pathogens. Intracellular pathogens are exposed to endogenous ROS as part of normal aerobic respiration, also aexogenous ROS and RNS are generated by the host immune system in response to infection. Nanoparticles which are designed for drug delivery are capable of trapping the desired drug in the particles which protects the drug from enzymatic degradation in a biological system. The small (subcellular) size of nanoparticles enables higher intracellular uptake of the drug which results in the reduction of the concentration of free drugs reducing their toxic effect. Research on the modulation of immune response and oxidative stress using nanoparticles used to encapsulate drugs has yet to be explored fully. In this review we illustrate the immune activation and generation of oxidative stress properties which are mediated by nanoparticle encapsulated drug delivery systems which can make the therapy more effective in case of diseases caused by intracellular pathogens.

Abstract Thyroid diseases have a complex and multifactorial aetiology. Despite the numerous studies on the signals referable to the malignant transition, still remain elusive the molecular mechanisms concerning the role of oxidative stress. Based on its strong oxidative power, H2O2 could be responsible for the high level of oxidative DNA damage observed in cancerous thyroid tissue and hyper-activation of mitogen-activated protein kinase (MAPK), and PI3K/Akt, that mediate ErbB signaling. Increased levels of 8-oxoG DNA adducts have been detected in the early stages of thyroid cancer. These DNA lesions are efficiently recognized and removed by the base excision repair (BER) pathway initiated by 8-oxoG glycosylase1 (OGG1). This study investigated the relationship between the EGFR and OGG1-BER pathways and their mutual regulation following oxidative stress stimulus by H2O2 in human thyrocytes. We clarified the modulation of ErbB receptors and their downstream pathways (PI3K / Akt and MAPK / ERK) under oxidative stress (from H2O2) at the level of gene and protein expression, according to the mechanism defined in a non-pathological cell system, Nthy-ori 3-1. Later, on the basis of the obtained results of gene expression cluster analysis in normal cells, we assessed the dysregulation of the relationships in a model of papillary thyroid cancer with RET/TPC rearrangement (TPC-1). Our observations demonstrated that a H2O2 stress may induce a physiological cross-regulation between ErbB and OGG1-BER pathways in normal thyroid cells (while this is dysregulated in the TPC-1 cells. Gene expression data also delineated that MUTYH gene could play a physiological role in cross-talk between ErbB and BER pathways and this function is instead lost in cancer cells. Overall our data about OGG1 protein expression suggest that the alternative splicing mechanisms may lead to different protein isoforms, physiologically regulated in response to ErbB modulation, and that these could be dysregulated in the progression of thyroid malignancies with RET/TPC rearrangement.

Lead (Pb) is a toxic environmental heavy metal that induces serious clinical defect on all organs with the nervous system being the primary target. Curcumin is the main active constituent of turmeric rhizome (Curcuma longa) with strong antioxidant and anti-inflammatory properties. This study is aimed at evaluating the therapeutic potentials of curcumin on Pb-induced neurotoxicity. Thirty six male Sprague Dawley rats were randomly assigned into five (5) groups with 12 rats in the control (normal saline) and 6 rats for the lead treated group (LTG) (50 mg/kg lead acetate for 4 weeks), recovery group (RC) (50 mg/kg lead acetate for 4 weeks), treatment group 1 (Cur100) (50 mg/kg lead acetate for 4 weeks, followed by 100 mg/kg curcumin for 4 weeks) and treatment group 2 (Cur200) (50 mg/kg lead acetate for 4 weeks, followed by 200 mg/kg curcumin for 4 weeks) groups each. All experimental groups received the oral treatments through orogastric-tube on alternate days. Motor function was assessed using horizontal bar method while Pb concentration in the cerebellum of the rats were evaluated using ICP-MS techniques. Pb-administered rats showed significant decrease in motor scores, SOD activity with increase MDA levels and Pb concentration in their cerebellum with marked alterations in the histological architecture of the cerebellar cortex layers. However, treatment with curcumin improved the motor score, reduced Pb concentration in the cerebellum and ameliorates the markers of oxidative stress as well as restored the histological architecture of the cerebellum. The results this in study suggested that curcumin attenuates Pb-induced neurotoxicity via inhibition of oxidative stress and chelating activity.

Lead (Pb) is a toxic environmental heavy metal that induces serious clinical defect on all organs with the nervous system being the primary target. Curcumin is the main active constituent of turmeric rhizome (Curcuma longa) with strong antioxidant and anti-inflammatory properties. This study is aimed at evaluating the therapeutic potentials of curcumin on Pb-induced neurotoxicity. Thirty six male Sprague Dawley rats were randomly assigned into five (5) groups with 12 rats in the control (normal saline) and 6 rats for the lead treated group (LTG) (50 mg/kg lead acetate for 4 weeks), recovery group (RC) (50 mg/kg lead acetate for 4 weeks), treatment group 1 (Cur100) (50 mg/kg lead acetate for 4 weeks, followed by 100 mg/kg curcumin for 4 weeks) and treatment group 2 (Cur200) (50 mg/kg lead acetate for 4 weeks, followed by 200 mg/kg curcumin for 4 weeks) groups each. All experimental groups received the oral treatments through orogastric-tube on alternate days. Motor function was assessed using horizontal bar method while Pb concentration in the cerebellum of the rats were evaluated using ICP-MS techniques. Pb-administered rats showed significant decrease in motor scores, SOD activity with increase MDA levels and Pb concentration in their cerebellum with marked alterations in the histological architecture of the cerebellar cortex layers. However, treatment with curcumin improved the motor score, reduced Pb concentration in the cerebellum and ameliorates the markers of oxidative stress as well as restored the histological architecture of the cerebellum. The results this in study suggested that curcumin attenuates Pb-induced neurotoxicity via inhibition of oxidative stress and chelating activity.

Field cricket (Gryllus bimaculatus) is newly emerged as an edible insect in several countries. Anti-inflammatory effect of glycosaminoglycan derived this cricket was not fully investigated on chronic disease animal model such as diabetic mouse. For potential therapeutic agents, anti-diabetic activities of field cricket glycosaminoglycan (GbG) was evaluated in diabetic mice based on their abilities to reduce glucose, ALT, AST, LDL-cholesterol, and BUN levels, compared with dung beetle (Catharsius molossus) glycosaminoglycan (CaG) as a positive control glycosaminoglycan. Db mice were orally administered for one month according to their groups: Db Hetero (normal), Db Homo (type-2 diabetic), CaG (5 mg/kg), GbG (5 mg/kg), and metformin (10 mg/kg). Blood glucose level was decreased after 1^st week treatment with GbG. It also inhibited LDL-cholesterol and alkaline phosphatase levels. Regarding oxidative damage of diabetic state, levels of hepatocellular biomarkers levels and protein carbonyl content were reduced in db mice treated with GbG. Especially anti-oxidative activities of catalase, superoxide dismutase, and glutathione peroxidase were significantly increased in GbG treated group compared to those in the control. GbG was composed of heparin disaccharides and main N-glycan was identified as Hex₉GlcNAc₂ (m/z 1905.7) of with neutral mono-sugar mainly comprising of hexose, L (+) rhamnose by mass spectroscopy. These results from sero-biochemical, hepatocellular anti-oxidant assay in db mice data suggest cricket (G. bimaculatus) glycosaminoglycan might play a role in its anti-diabetic action.

Shiga toxin (Stx) produced by Escherichia coli is the main pathogenic factor of diarrhea-associated hemolytic uremic syndrome (HUS), which is characterized by obstruction of renal microvasculature by platelet-fibrin thrombi. It is well known that the oxidative imbalance generated by Stx induces platelet activation, contributing to thrombus formation. Moreover, activated platelets release soluble CD40 ligand (sCD40L) which in turn contributes to oxidative imbalance, triggering the release of reactive oxidative species (ROS) on various cellular types. The aim of this work was to determine if the interaction between the oxidative response and platelet-derived sCD40L participates in the pathogenic mechanism during HUS. Activated human glomerular endothelial cells (HGEC) by Stx2 induced platelets to adhere to them. Although platelet adhesion did not contribute to endothelial damage, high levels of sCD40L were released to the medium. The release of sCD40L by activated platelets was inhibited by antioxidant treatment. Furthermore, we found increased levels of sCD40L in plasma from HUS patients, which were also able to trigger the respiratory burst in monocytes, in a sCD40L-dependent manner. Thus, we concluded that platelet-derived sCD40L and the oxidative response are reciprocally stimulated during Stx2-associated HUS. This process may contribute to the evolution of glomerular occlusion and the microangiopathic lesions.

Oxidative and nitrosative stress are a common problem when manipulating gametes in vitro. In vitro development in mammalian embryos is highly affected by culture conditions, especially by reactive oxygen species (ROS) and reactive nitrogen species (RNS), because its absence or over production causes embryo arrest and changes in gene expression. Melatonin in gamete co-incubation during IVF has deleterious or positive effects depending on the concentration used in culture medium, demonstrating the delicate balance that must exist between antioxidant and pro-oxidant activity. Further research is needed to better understand the possible impact of melatonin on the different IVP steps in domestic animals, especially in seasonal breeds where this neuro-hormone system highly regulates its reproduction physiology.

Chamazulene (CA) is an intensely blue molecule with a wealth of biological properties. In cosmetics chamazulene is exploited as a natural coloring and soothing agent. CA is unstable and tends to spontaneous degradation accelerated by light. We studied the photodegradation of CA upon controlled exposure to UVB-UVA irradiation by multi-ple techniques, including GC-MS, UHPLC-PDA-ESI-MS/MS and by direct infusion in ESI-MSn, which were matched to in silico mass spectral simulations to identify degra-dation products. Seven byproducts formed upon UVA exposure for 3 h at 70mW/cm2 (blue-to-green color change) were identified, including CA dimers and CA benzenoid which were not found on extended 6 h irradiation (green-to-yellow fading). Photosta-bility tests with reduced irradiance conducted in various solvents in the pres-ence/absence of air indicated highest degradation in acetonitrile in the presence of ox-ygen, suggesting a photo-oxidative mechanism. Testing in the presence of antioxidants (tocopherol, ascorbyl palmitate, hydroxytyrosol, bakuchiol, γ-terpinene, TEMPO and their combinations) indicated highest protection by tocopherol and TEMPO. Sun-screens ethylhexyl methoxycinnamate and particularly Tinosorb® S (but not octo-crylene) showed good CA photoprotection. Thermal stability tests indicated no degra-dation of CA in acetonitrile at 50°C in the dark for 50 days; however, accelerated deg-radation occurred in the presence of ascrorbyl palmitate.

A meta-analysis showed a significant association between activated immune-inflammatory and nitro-oxidative (IO&NS) pathways and suicide attempts (SA). There are no data whether suicidal ideation (SI) is accompanied by activated IO&NS pathways and whether there are differences between SA and SI. The current study searched PubMed, Google Scholar, and Web of Science, for articles published from inception until May 10, 2021, and systematically reviewed and meta-analyzed the association between recent SA/SI (< 3 months) and IO&NS biomarkers. We included studies which compared psychiatric patients with and without SA and SI and controls (either healthy controls or patients without SA or SI) and used meta-analysis (random-effect model with restricted maximum-likelihood) to delineate effect sizes with 95% confidence intervals (CI). Our search included 59 studies comprising 4.034 SA/SI cases and 12.377 controls. Patients with SA/SI showed activated IO&NS pathways (SMD: 0.299; CI: 0.200; 0.397) when compared to controls. The immune profiles were more strongly associated with SA than with SI, particularly when compared to healthy controls, as evidenced by activated IO&NS pathways (SMD: 0.796; CI: 0.503; 1.089), an immune-inflammatory response (SMD: 1.409; CI: 0.637; 1.462), inflammation (SMD: 1.200; CI: 0.584; 1.816), and neurotoxicity (SMD: 0.904; CI: 0.431; 1.378). The effects sizes of the IO&NS, immune-inflammatory response and inflammatory profile were significantly greater in SA than in SI. In conclusion: increased neurotoxicity due to inflammation and nitro-oxidative stress and lowered neuroprotection may explain at least in part why psychiatric patients show increased SA and SI. The IO&NS pathways are more pronounced in recent SA than in SI.

Intrauterine growth restriction (IUGR) and being born small for gestational age (SGA) are two distinct conditions with different implications for child development. IUGR is associated with greater perinatal morbidity and mortality and can be identified by additional abnormalities (pathological Doppler sonography, oligohydramnios, lack of growth in the interval, estimated weight <3rd percentile). IUGR may also be present in neonates with birth weights above the 10th percentile. Recognizing fetuses being “at risk” of a higher perinatal mortality and morbidity rate in order to monitor them accordingly and deliver them in good time is still challenging. This review article summarizes approaches to increase the diagnostic accuracy of IUGR and presents current concepts of pathophysiology with a focus on oxidative stress and consecutive inflammatory and metabolic changes. Since prenatal influences affect the risk of later diseases, we also discuss the need for interdisciplinary follow-up strategies during childhood and look at future scientific challenges. It should be emphasized that prenatal and postnatal care of IUGR neonates should be regarded as a continuum.

Lupus nephritis (LN) is a severe complication of systemic lupus erythematosus (SLE) and is considered one of the leading causes of mortality. Multiple immunological pathways are involved in the pathogenesis of SLE, which makes it imperative to deepen our knowledge about this disease's immunopathological complexity and explore new therapeutic targets. Since an altered redox state contributes to immune system dysregulation, this document briefly addresses the role of oxidative stress (OS), oxidative DNA damage, antioxidant enzymes, mitochondrial function, and mitophagy in SLE and LN. Although adaptive immunity's participation in the development of autoimmunity is undeniable, increasing data emphasize the importance of innate immunity elements, particularly the Toll-like receptors (TLRs) that recognize nucleic acid ligands, in inflammatory and autoimmune diseases. Here, we discuss the intriguing role of TLR7 and TLR9 in developing SLE and LN. Also included are the essential characteristics of conventional treatments and some other novel and little-explored alternatives that offer options to improve renal function in LN.

Chronic obstructive pulmonary disease (COPD) is a respiratory disease associated with airways inflammation and lung parenchyma fibrosis. The primary goals of COPD treatment are to re-duce symptoms and risk of exacerbations, therefore pulmonary rehabilitation is considered the key component of managing COPD patients. Oxidative airway damage, inflammation and re-duction of endogenous antioxidant enzymes are known to play a crucial role in the pathogenesis of COPD. Natural antioxidants have also recently been considered as they play an important role in metabolism, DNA repair and fighting the effects of oxidative stress. In this paper we evaluated the response of 105 elderly COPD patients to pulmonary rehabilitation (PR), based on high or low vegetable consumption, by analyzing clinical parameters and biological measure-ments at baseline and after completion of the three weeks PR. We found that high vegetable in-take in normal diet, without any specific intervention, can increase the probability to success-fully respond to rehabilitation (65.4% of responders ate vegetables daily vs. 40.0% of Non-Responders, p=0.033). Three weeks of pulmonary rehabilitation are probably too short to reveal a reduction of the oxidative stress and DNA damage, but are enough to show an im-provement in the patient's inflammatory state.

Epigallocatechin-3-gallate (EGCG) is the most abundant polyphenol in green tea. In this study, the effects of dietary EGCG on oxidative stress and the metabolism and toxicity of acetaminophen in liver were investigated. Rats were fed the diets with (0.54 %) or without EGCG supplementation for four weeks and were then intraperitoneally injected with acetaminophen (1g/kg). Results showed EGCG lowered hepatic oxidative stress and cytochrome P450 (CYP) 1A2, 2E1, and 3A, and UDP-glucurosyltransferase activities prior to acetaminophen injection. After acetaminophen challenge, the elevations in plasma alanine aminotransferase activity and histological changes in liver were ameliorated by EGCG treatment. EGCG reduced acetaminophen-induced apoptosis by increasing the Bax/Bcl2 ratio in liver. EGCG mildly increased autophagy by increasing the LC3B II/I ratio. Lower hepatic acetaminophen-glutathione and acetaminophen-protein adducts contents were observed after EGCG treatment. EGCG increased glutathione peroxidase and NAD(P)H quinone 1 oxidoreductase activities and reduced organic anion-transporting polypeptides 1a1 expression in liver after acetaminophen treatment. Our results indicate that EGCG may lower oxidative stress and reduce the metabolism and toxicity of acetaminophen. The reductions in CYP-mediated acetaminophen bioactivation and uptake transporter, as well as enhanced antioxidant enzyme activity, may limit the accumulation of toxic products in liver and thus lower hepatotoxicity

Inhaled particulate matter (PM) is a key player in the millions of yearly deaths worldwide related to air pollution. The oxidative potential of PM provides an indication of its ability to promote an oxidative environment. When the human lungs are exposed to PM, the reactive oxygen species (ROS) generated in such oxidative environment, if excessive, may lead to cell damage via oxidative stress. Inflammation, endoplasmic reticulum stress, airway remodeling, and many different cell death modes (apoptosis, ferroptosis, pyroptosis, among others) can be triggered by oxidative stress via complex molecular pathways, which also involve the adaptive cellular response. But ROS can also directly interact with macromolecules such as proteins and lipids, as well as nucleic acids, having been reported to induce DNA damage and epigenetic modifications, which jeopardizes homeostasis. These facts have been extensively studied in in vitro models and confirmed in in vivo models.In this review, we delve beyond conventional assessments of airborne particles, discussing their oxidative potential and the PM-induced ROS-mediated cellular damage observed in in vitro models. The close link between oxidative stress and inflammation, and the manifestation of different cell death modes is highlighted by reviewing the latest literature. The effects of ROS on the balance of DNA damage and repair, carcinogenicity and epigenetics interplay are then analyzed. Finally, we expand on the latest reports on the antioxidants’ potential to counteract the deleterious effects of ROS, and disclose future perspectives for the topic.

Although a slight imbalance between oxidative and antioxidative mediators is part of normal physiology that enables cell aging and the removal of dead cells, burns disturb this equilibrium locally and systemically. Topical burn dressings may attenuate local and systemic oxidative stress and positively influence the post-burn clinical course. This review integrated knowledge regarding the impact of burn dressings on oxidative stress. Using keywords and in-text searches, literature was identified from PubMed, Google Scholar, and Google articles, and studies on local or topical applications of wound dressings and associated oxidative stress were selected. As im-balances between oxidative mediators and antioxidative agents significantly contribute to organ dysfunction and healing disturbance, we investigated oxidative stress on organs, metabolic changes, clinical results, and oxidative parameters influenced by applied dressings. We found positive local and systemic effects of external burn dressings in laboratory and animal tests; however, such studies were rare in humans. Nevertheless, we identified successful cases of semi-occlusive, occlusive, and biologically active dressings that reduce oxidative stress in hu-man burns. In particular, we highlight promising clinical and laboratory results from lac-tate-releasing dressings. Our review provides an invaluable resource for future development and clinical applications of burn dressings.

Carbon dioxide has become a global challenge, where the emissions have become more than what could be handled. In this regard, conversion of CO2 to value added chemicals and thus recycling CO2 became a viable option. One of these options is the use of a process in strong development: oxycombustion. However, the gases resulting from this process contain some traces of impurities that can hinder the recovery of CO2 such as NO and CO. This work has therefore focused on the study of the reaction of NO reduction by CO in an oxidizing medium, using catalytic materials based on various supported noble metals. These materials were extensively characterized by a variety of methods including BET surface area measurements, hydrogen chemisorption, Transmission Electron Microscopy (TEM) and H2 temperature programmed reduction (H2-TPR). The obtained results show that the catalytic behaviour of M/Al2O3 catalysts in CO oxidation and NO reduction with CO in oxidative conditions depends mainly on the nature of the metal. The best result for these both reactions is obtained with Pt/Al2O3 catalyst. The Pt nanoparticles existing in the metallic form (Pt°) showed by TPR could explain the activity.