Consequence Of Oxidative Stress Research Articles

Microdroplet-SERS platform for single cell-secreted VEGF and extracellular pH analysis in oxidative stress event

Although oxidative stress processes based on reactive oxygen species have been the research focus, analyzing this phenomenon at the single-cell level is challenging. A microfluidic platform combined with highly sensitive surface-enhanced Raman scattering (SERS) technology was constructed. The secretion of the vascular endothelial growth factor (VEGF) and the extracellular microenvironmental pH fluctuations of a single cell during the oxidative stress process were assessed and analyzed. The immune sandwich structure formed between the capture probe and the reporter probe with the linkage of secreted VEGF was built above the probed cell surface in each drop. The self-driven collection behavior of the magnetic bead-based capture probe toward the cell surface significantly amplified the SERS signals of the reporter probe, thus improving the sensitivity and accuracy of detection. 4-Mercaptopyridine (4-Mpy) responding sensitively to pH was applied to label the reporter probe, which endows the extracellular microenvironmental pH sensing during oxidative stress events according to relative SERS intensity. Combined with machine learning to analyze the spectral characteristics, the distinction between normal cells and different types of tumor cells was finally realized. This study makes full use of the advantages of machine learning to process spectral data to explore deep information and provides an auxiliary tool for diagnosing cancer and other medical conditions in the future.

In vitro evidence of antioxidant and anti-inflammatory effects of a new nutraceutical formulation explains benefits in a clinical setting of COPD patients.

Background and Aim: Increased oxidative stress within the airways is associated to epithelial damage and amplification of inflammatory responses that in turn contribute to Chronic Obstructive Pulmonary Disease (COPD) progression. This study was aimed to identify whether a new formulation of N-acetylcisteine (NAC), carnitine, curcumin and B2 vitamin could counteract oxidative stress and downstream pro-inflammatory events promoted by cigarette smoke extract (CSE) exposure in primary bronchial epithelial cells (PBEC), both submerged/undifferentiated (S-PBEC) and cultured at the air-liquid interface (ALI-PBEC). Methods: PBEC were exposed to CSE with/without the new formulation or NAC alone and ROS production, IL-8 and IL-6 gene expression and protein release were evaluated. Results: CSE increased ROS, IL-8 and IL-6 gene expression and protein release and the new formulation counteracted these effects. NAC alone was not effective on IL-8 and IL-6 release. The effects of a similar nutraceutical formulation were evaluated in COPD patients treated for six months. The results showed that the treatment reduced the concentration of IL-8 in nasal wash and improved quality of life. Conclusion: The tested formulation, exerting antioxidant and anti-inflammatory effects, can preserve airway epithelial homeostasis and improve clinical symptoms in COPD.

Anion exchanger1 (AE1/SLC4A1) function is impaired in red blood cells from prediabetic subjects: Potential benefits of finger lime (Citrus australasica, Faustrime cultivar) juice extract.

Prediabetes is a risk state that defines a high chance of developing diabetes and cardiovascular disease. Oxidative stress mediated by hyperglycemia-induced production of reactive species could play a crucial role in this context. In the present study, we investigated whether the anion exchange capability mediated by AE1 (SLC4A1), which is sensitive to oxidative stress, was altered in human red blood cells (RBCs) obtained from prediabetic volunteers. In addition, we assessed the precise composition of bioactive compounds and the potential benefits of finger lime juice extract (Citrus australasica, Faustrime cultivar) in counteracting oxidative stress-related functional alterations. Human RBCs from normal and prediabetic volunteers were incubated with 50 µg/mL juice extract for 2 h at 25°C. Juice extract restored alterations of the anion exchange capability mediated by AE1 and prevented the structural rearrangements of AE1 and α/β-spectrin in prediabetic RBCs. AE1 functional and structural alterations were not associated with an increase in lipid peroxidation or protein oxidation at the level of the plasma membrane. An increased production of intracellular ROS, which provoked the oxidation of hemoglobin to methemoglobin, both reverted by juice extract, was instead observed. Importantly, juice extract also induced a reduction in glycated hemoglobin levels in prediabetic RBCs. Finally, juice extract blunted the overactivation of the endogenous antioxidant enzymes catalase and superoxide dismutase and prevented glutathione depletion in prediabetic RBCs. These findings contribute to clarifying cellular and molecular mechanisms related to oxidative stress and glycation events that may influence RBC and systemic homeostasis in prediabetes, identify AE1 as a sensitive biomarker of RBC structural and function alterations in prediabetes and propose finger lime juice extract as a natural antioxidant for the treatment and/or prevention of the complications associated with the prediabetic condition.

The emerging role of oxidative stress in inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a chronic immune-mediated condition that affects the digestive system and includes Crohn's disease (CD) and ulcerative colitis (UC). Although the exact etiology of IBD remains uncertain, dysfunctional immunoregulation of the gut is believed to be the main culprit. Amongst the immunoregulatory factors, reactive oxygen species (ROS) and reactive nitrogen species (RNS), components of the oxidative stress event, are produced at abnormally high levels in IBD. Their destructive effects may contribute to the disease's initiation and propagation, as they damage the gut lining and activate inflammatory signaling pathways, further exacerbating the inflammation. Oxidative stress markers, such as malondialdehyde (MDA), 8-hydroxy-2'-deoxyguanosine (8-OHdG), and serum-free thiols (R-SH), can be measured in the blood and stool of patients with IBD. These markers are elevated in patients with IBD, and their levels correlate with the severity of the disease. Thus, oxidative stress markers can be used not only in IBD diagnosis but also in monitoring the response to treatment. It can also be targeted in IBD treatment through the use of antioxidants, including vitamin C, vitamin E, glutathione, and N-acetylcysteine. In this review, we summarize the role of oxidative stress in the pathophysiology of IBD, its diagnostic targets, and the potential application of antioxidant therapies to manage and treat IBD.

Melatonin as a natural anti-inflammatory and anti-oxidant therapy in the testis: a focus on infertility and aging†.

Melatonin is a pineal hormone that regulates testicular activity (i.e., steroidogenesis and spermatogenesis) through two complementary mechanisms, indirect effects exerted via the hypothalamic-adenohypophyseal axis and direct actions that take place on the different cell populations of the male gonad. The effects of increased age on the testis and the general mechanisms involved in testicular pathology leading to infertility are still only poorly understood. However, there is growing evidence that link testicular aging and idiopathic male infertility to local inflammatory and oxidative stress events. Because literature data strongly indicate that melatonin exhibits anti-inflammatory and anti-oxidant properties, this review focuses on the potential benefits exerted by this indoleamine at testicular level in male reproductive fertility and aging. Taking into account that the effects of melatonin supplementation on testicular function are currently being investigated, the overview covers not only promising prospects but also many questions concerning the future therapeutic value of this indoleamine as an anti-aging drug as well as in the management of cases of male infertility for which there are no medical treatments currently available.

Extracellular vesicles activated cancer-associated fibroblasts promote lung cancer metastasis through mitophagy and mtDNA transfer.

Studies have shown that oxidative stress and its resistance plays important roles in the process of tumor metastasis, and mitochondrial dysfunction caused by mitochondrial DNA (mtDNA) damage is an important molecular event in oxidative stress. In lung cancer, the normal fibroblasts (NFs) are activated as cancer-associated fibroblasts (CAFs), and act in the realms of the tumor microenvironment (TME) with consequences for tumor growth and metastasis. However, its activation mechanism and whether it participates in tumor metastasis through antioxidative stress remain unclear. The role and signaling pathways of tumor cell derived extracellular vesicles (EVs) activating NFs and the characteristic of induced CAFs (iCAFs) were measured by the transmission electron microscopy, nanoparticle tracking analysis, immunofluorescence, collagen contraction assay, quantitative PCR, immunoblotting, luciferase reporter assay and mitochondrial membrane potential detection. Mitochondrial genome and single nucleotide polymorphism sequencing were used to investigate the transport of mtDNA from iCAFs to ρ0 cells, which were tumor cells with mitochondrial dysfunction caused by depletion of mtDNA. Further, the effects of iCAFs on mitochondrial function, growth and metastasis of tumor cells were analysed in co-culture models both in vitro and in vivo, using succinate dehydrogenase, glutathione and oxygen consumption rate measurements, CCK-8 assay, transwell assay, xenotransplantation and metastasis experiments as well as in situ hybridization and immunohistochemistry. Our findings revealed that EVs derived from high-metastatic lung cancer cells packaged miR-1290 that directly targets MT1G, leading to activation of AKT signaling in NFs and inducing NFs conversion to CAFs. The iCAFs exhibit higher levels of autophagy and mitophagy and more mtDNA release, and reactive oxygen species (ROS) could further promote this process. After cocultured with the conditioned medium (CM) of iCAFs, the ρ0 cells may restore its mitochondrial function by acquisition of mtDNA from CAFs, and further promotes tumor metastasis. These results elucidate a novel mechanism that CAFs activated by tumor-derived EVs can promote metastasis by transferring mtDNA and restoring mitochondrial function of tumor cells which result in resistance of oxidative stress, and provide a new therapeutic target for lung cancer metastasis.

Comparative effectiveness of nitro dihydrocapsaicin, new synthetic derivative capsaicinoid, and capsaicin in alleviating oxidative stress and inflammation on lipopolysaccharide-stimulated corneal epithelial cells

Loss of tear homeostasis, characterized by hyperosmolarity of the ocular surface, induces cell damage through inflammation and oxidation. Transient receptor potential vanilloid 1 (TRPV1), a sensor for osmotic changes, plays a crucial role as a calcium ion channel in the pathogenesis of hypertonic-related eye diseases. Capsaicin (CAP), a potent phytochemical, alleviates inflammation during oxidative stress events by activating TRPV1. However, the pharmacological use of CAP for eye treatment is limited by its pungency. Nitro dihydrocapsaicin (NDHC) was synthesized with aromatic ring modification of CAP structure to overcome the pungent effect. We compared the molecular features of NDHC and CAP, along with their biological activities in human corneal epithelial (HCE) cells, focusing on antioxidant and anti-inflammatory activities. The results demonstrated that NDHC maintained cell viability, cell shape, and exhibited lower cytotoxicity compared to CAP-treated cells. Moreover, NDHC prevented oxidative stress and inflammation in HCE cells following lipopolysaccharide (LPS) administration. These findings underscore the beneficial effect of NDHC in alleviating ocular surface inflammation, suggesting that NDHC may serve as an alternative anti-inflammatory agent targeting TRPV1 for improving hyperosmotic stress-induced ocular surface damage.

Deletion of Glyoxalase 1 Exacerbates Acetaminophen-Induced Hepatotoxicity in Mice.

Acetaminophen (APAP) overdose triggers a cascade of intracellular oxidative stress events, culminating in acute liver injury. The clinically used antidote, N-acetylcysteine (NAC), has a narrow therapeutic window, and early treatment is essential for a satisfactory therapeutic outcome. For more versatile therapies that can be effective even at late presentation, the intricacies of APAP-induced hepatotoxicity must be better understood. Accumulation of advanced glycation end products (AGEs) and the consequent activation of the receptor for AGEs (RAGE) are considered one of the key mechanistic features of APAP toxicity. Glyoxalase 1 (Glo-1) regulates AGE formation by limiting the levels of methylglyoxal (MEG). In this study, we studied the relevance of Glo-1 in the APAP-mediated activation of RAGE and downstream cell death cascades. Constitutive Glo-1-knockout mice (GKO) and a cofactor of Glo-1, ψ-GSH, were used as tools. Our findings showed elevated oxidative stress resulting from the activation of RAGE and hepatocyte necrosis through steatosis in GKO mice treated with high-dose APAP compared to wild-type controls. A unique feature of the hepatic necrosis in GKO mice was the appearance of microvesicular steatosis as a result of centrilobular necrosis, rather than the inflammation seen in the wild type. The GSH surrogate and general antioxidant ψ-GSH alleviated APAP toxicity irrespective of the Glo-1 status, suggesting that oxidative stress is the primary driver of APAP toxicity. Overall, the exacerbation of APAP hepatotoxicity in GKO mice suggests the importance of this enzyme system in antioxidant defense against the initial stages of APAP overdose.

The Standardized Extract of Centella asiatica and Its Fractions Exert Antioxidative and Anti-Neuroinflammatory Effects on Microglial Cells and Regulate the Nrf2/HO-1 Signaling Pathway.

Neuroinflammation and oxidative stress can aggravate the progression of Alzheimer's disease (AD). Centella asiatica has been traditionally consumed for memory and cognition. The triterpenes (asiaticoside, madecassoside, asiatic acid, madecassic acid) have been standardized in the ethanolic extract of Centella asiatica (SECA). The bioactivity of the triterpenes in different solvent polarities of SECA is still unknown. In this study, the antioxidative and anti-neuroinflammatory effects of SECA and its fractions were explored on lipopolysaccharides (LPS)-induced microglial cells. HPLC measured the four triterpenes in SECA and its fractions. SECA and its fractions were tested for cytotoxicity on microglial cells using MTT assay. NO, pro-inflammatory cytokines (TNF-α, IL-6, IL-1β), ROS, and MDA (lipid peroxidation) produced by LPS-induced microglial cells were measured by colorimetric assays and ELISA. Nrf2 and HO-1 protein expressions were measured using western blotting. The SECA and its fractions were non-toxic to BV2 microglial cells at tested concentrations. The levels of NO, TNF-α, IL-6, ROS, and lipid peroxidation in LPS-induced BV2 microglial cells were significantly reduced (p < 0.001) by SECA and its fractions. SECA and some of its fractions can activate the Nrf2/HO-1 signaling pathway by significantly enhancing (p < 0.05) the Nrf2 and HO-1 protein expressions. This study suggests that the inhibitory activity of SECA and its fractions on pro-inflammatory and oxidative stress events may be the result of the activation of antioxidant defense systems. The potential of SECA and its fractions in reducing neuroinflammation and oxidative stress can be further studied as a potential therapeutic strategy for AD.

Voacangine mitigates oxidative stress and neuroinflammation in middle cerebral artery occlusion-induced cerebral ischemia/reperfusion injury by averting the NF-κBp65/MAPK signaling pathways in rats.

Ischemic stroke is a leading cause of human mortality. Cerebral ischemia-reperfusion injury (CI/RI) is a primary cause of stroke. Ischemia-reperfusion (I/R) resulting in oxidative stress and inflammatory events may lead to severe neuronal impairments. Thus, anti-oxidative and anti-inflammatory mediators that can alleviate post-I/R neuronal injuries are required for the treatment of CI/RI. An alkaloid, voacangine (VCG) is a recognized antioxidant, anti-inflammatory, and anticancer agent. Hence, the current study intended to explore the neuroprotective potential and the principal mechanisms of VCG in CI/RI. The experimental rats were divided into four sets: control, I/R-induced, I/R + VCG (2.5 mg/kg), I/R + VCG (5 mg/kg). CI/RI was induced by implanting a thread into the middle cerebral artery occlusion (MCAO) model. Brain damages were assessed on the basis of brain edema, brain infarct volume, neurological deficit score, histopathology, oxidative stress, and neuroinflammation. Results revealed that VCG inhibited the triggering of NLRP3 inflammasome, pro-inflammatory cytokines, lipid peroxidation, but enhanced the antioxidant status in MCAO rats. Furthermore, VCG treatment averted brain damage by I/R, neuroinflammation, and oxidative stress by suppressing NF-κBp65/MAPK pathways. The results of the study provide pertinent insights pertaining to the role of VCG as a potential neuroprotective agent against ischemic stroke.

Beneficial role of amygdalin extracts against animal growth regulator Boldjan induced cardiac toxicity, injury and oxidative stress in male rats.

Millions of individuals have used illicit anabolic-androgenic steroids (AAS), but the long-term cardiovascular associations of these drugs remain incompletely understood. Boldjan is AAS medication which is used in veterinary medicine and by young adults aiming to have a better appearance improving their self-esteem. Therefore; the objective of the current investigation was to examine any potential preventative effects of amygdalin extract against anabolic steroid Boldjan induced cardic toxicity, injury and oxidative stress in male rat. Forty adult male Wistar rats were classified into five groups (Gp1, Control Gp; Gp2, Amygdalin Gp in which rats treated with amygdalin (100mg/kg body weight/day) daily for 2weeks; Gp3, Boldjan Gp in which rats treated with Boldjan (10mg/Kg BW/week) for 4weeks; Gp4, Boldjan+Amygdalin). Boldjan induced a significant rises in serum lactate dehydrogenase (LDH), creatine kinase (CK) and creatine kinase MB (CK MB), aspartate aminotransferase (AST), total cholesterol (TC), triglycerides (TG), low-density lipoprotein-cholesterol (LDL-C), and very-low-density lipoprotein-cholesterol (VLDL-C), cardiac injury, and malondialdehyde (MDA) levels and a significant depletion in serum high-density lipoprotein-cholesterol (HDL-C), cardiac reduced glutathione (GSH), Superoxide dismutase (SOD) and catalase (Cat) activities as compared to control Gp. In contrast, Amygdalin significantly reversed the Boldjan induced cardiac toxicity in post treated rats Gp (Boldjan+Amygdalin). Amygdalin could be an efficient preventive supplement for mitigating Boldjan induced cardiac toxicity, possibly via controlling oxidative stress events.

Prenatal Alcohol Exposure and Metabolic Disorders in Pediatrics: The Role of the Oxidative Stress-A Review of the Literature.

Prenatal alcohol exposure is responsible for increasing chronic disease risk in later life, including obesity and metabolic syndrome. Alcohol drinking may compromise endogenous antioxidant capacity, causing an increase in free radicals and reactive oxygen species in the newborn. Excessive reactive oxygen species could attack the cellular proteins, lipids, and nucleic acids, leading to cellular dysfunction. Moreover, oxidative stress could play a crucial role in the altered synthesis and release of neurotrophins and progressive mitochondrial modifications with uncontrolled apoptosis. This narrative review aims to underline the important role of alcohol abuse in oxidative stress events and consequent metabolic and neurocognitive impairments in children exposed to alcohol during gestational life.

Neuroprotective Potential of Total Extract of Ulva Lactuca: An In vitro study

Alzheimer's disease (AD) is mainly general form of dementia that is linked to the increase of extracellular amyloid beta (Aβ) plaques. Oxidative stress and neurotoxicity events that are linked to the aetiology of AD have been postulated to be influenced by genetic, environmental, and dietary variables. Using the use of in vitro models, we attempted to determine whether or not Ulva lactuca had antioxidant and neuroprotective properties. SH-SY5Y The research employed pre-existing Neuroblastoma cell lines. Caspase 3 expression was also determined to know the level of protection of neuronal cells. Our results showed that the total extract of UL effectively reduced cell death and caspase 3 levels were also decreased in the cells treated with TEUL. The extract also has effective antioxidant properties proved. Further, it was also proved that the extract also has acetylcholinesterase enzyme inhibitory activity which is essential in treating AD.

Immune response to zinc oxide inhalation in metal fume fever, and the possible role of IL-17f

Metal fume fever (MFF) is a work-related disease caused by the inhalation of metal particles, including zinc oxide. Chronic asthma may develop as a long-term consequence of exposure, particularly for welders and metal workers who are most at risk. In this study, we investigated the effects of ZnO fume inhalation on multiple inflammation-related cytokine- and cytokine receptor genes in mice from lung and lymph node samples, to explore the role of these in the pathogenesis of MFF. In our experiments, the animals were treated with a sub-toxic amount of ZnO fume for 4 h a day for 3 consecutive days. Sampling occurred 3 and 12 h post-treatment. We are the first to demonstrate that ZnO inhalation causes extremely increased levels of IL-17f gene expression at both sampling time points, in addition to increased gene expression rates of several other interleukins and cytokines, such as IL-4, IL-13, CXCL5, CSF-3, and IFN-γ. Our animal experiment provides new insights into the immunological processes of early metal fume fever development. IL-17f plays a crucial role in connecting immunological and oxidative stress events. The increased levels of IL-4 and IL-13 cytokines may explain the development of long-term allergic asthma after exposure to ZnO nanoparticles, which is well-known among welders, smelters, and metal workers.

Low-grade endotoxemia, oxidative stress and thrombotic events in patients with primary antiphospholipid syndrome

Abstract Introduction The persistence of antiphospholipid antibodies (aPL) is associated with a procoagulant state that could precipitate thrombotic events in the presence of a second pro-inflammatory stimulus, realizing thus the antiphosholipid syndrome (APS). Circulating lipopolysaccharide (LPS) is associated with systemic inflammation, enhanced oxidative stress and cardiovascular events in different clinical conditions, however, its presence and significance has not been evaluated in APS. Purpose To investigate the relationship between LPS, oxidative stress markers and risk of thrombotic events in the prospective multicenter ATHERO-APS study. Methods Baseline serum levels comparison of LPS, soluble NADPH oxidase 2-derived peptide (sNOX-dp), H2O2 production, hydrogen peroxide breakdown activity (HBA), and nitric oxide (NO) bioavailability in 97 primary APS (PAPS), 20 aPL carriers and 20 healthy controls (CTRL) matched for age, sex and BMI. In patients with high LPS levels, Cox-regression analysis was performed to assess the risk for a composite outcome of cardiovascular death, venous (VTE) and arterial thromboembolism (ATE). Results In the whole population (median age 51 (IQR: 45-61) years, 72% female), LPS levels were inversely correlated with HBA (Rs: -0.231, p=0.009) and NO (rS: -0.286, p=0.001) and directly correlated with sNOX-dp (rS:0.423, p&amp;lt;0.001) and H202 (rS: 0.211, p=0.017) (Table 1). Patients with PAPS showed a significant increased levels of LPS, sNOX-dp and H2O2 and a significant lower level of NO and HBA compared to aPL carriers and healthy CTRL. No correlation was found between LPS levels and anti-cardiolipin (aCL) IgG/IgM, anti-beta-2-Glycoprotein-I (aβ2GPI) IgG/IgM and lupus anticoagulant (LAC). After a median follow-up of 4.7 (4.1-5.6) years, 11 composite outcomes were reported: 1 cardiovascular death (stroke related), 3 ischemic strokes, 2 myocardial infarctions, 3 peripheral ATE and 2 VTE. Patients with basal LPS levels above the median value (&amp;gt;20.1 pg/ml) showed a higher annual incidence of composite outcome compared to those with LPS levels below the median value (4.0% vs 0.7%, p=0.013). On Cox-regression analysis, PAPS patients with LPS above the median value showed a 5-fold increased risk of composite outcome compared to patients with LPS below the median value, after adjustment for age, sex, aCL IgG, aβ2GPI IgG and LAC (Figure 1). Conclusion These preliminary data suggest that in PAPS, LPS is associated with a higher risk for a composite outcome of cardiovascular death, ATE and VTE. Further studies are needed to know which pharmacological approach may counteract the prothrombotic effect of LPS.

Gamma-glutamyl transpeptidase and indirect bilirubin may participate in systemic inflammation of patients with psoriatic arthritis

BackgroundPrevious studies have suggested that systemic metabolic abnormalities are closely related to psoriatic arthritis (PsA). Gamma-glutamyl transpeptidase (GGT) and indirect bilirubin (IBIL), two essential active substances in hepatic metabolism that have been demonstrated as an oxidative and anti-oxidative factor respectively, have been proved to be involved in oxidative stress damage and inflammation in several human diseases. However, their role in PsA remains unclear.MethodsIn this retrospective comparative cohort study, a case group of 68 PsA patients and a control group of 73 healthy volunteers from the Third Hospital of Hebei Medical University were enrolled. Serum GGT, IBIL, GGT/IBIL ratio and C-reactive protein (CRP), a well applied bio-marker of systemic inflammatory in PsA, were compared between the two groups. Furthermore, the relationship of GGT, IBIL and GGT/IBIL with CRP were explored in PsA patients. Finally, the patients were divided into high inflammation group and low inflammation group according to the median value of CRP. Multivariate logistic regression analyses were used for the association of systemic inflammation level with GGT, IBIL and GGT/IBIL.ResultsCompared with healthy controls, PsA patients exhibited significantly higher serum GGT, GGT/IBIL, and CRP levels and lower IBIL levels. Serum GGT and GGT/IBIL were positively correlated with CRP, whereas IBIL were negatively correlated with CRP. Binary logistic regression analysis revealed that serum GGT was a risk factor for high CRP in PsA, whereas IBIL was a protective factor. Furthermore, GGT/IBIL was a better indicator of high CRP condition in PsA patients than either GGT or IBIL alone, as determined by the receiver operating characteristic curves.ConclusionGGT and IBIL may participate in the pathogenesis of PsA. Additionally, GGT, IBIL and the balance of the two may reflect systemic inflammation mediated by oxidative stress events related to metabolic abnormalities to a certain extent.

Catalase from the Antarctic Fungus Aspergillus fumigatus I-9-Biosynthesis and Gene Characterization.

Extremely cold habitats are a serious challenge for the existing there organisms. Inhabitants of these conditions are mostly microorganisms and lower mycetae. The mechanisms of microbial adaptation to extreme conditions are still unclear. Low temperatures cause significant physiological and biochemical changes in cells. Recently, there has been increasing interest in the relationship between low-temperature exposure and oxidative stress events, as well as the importance of antioxidant enzymes for survival in such conditions. The catalase is involved in the first line of the cells' antioxidant defense. Published information supports the concept of a key role for catalase in antioxidant defense against cold stress in a wide range of organisms isolated from the Antarctic. Data on representatives of microscopic fungi, however, are rarely found. There is scarce information on the characterization of catalase synthesized by adapted to cold stress organisms. Overall, this study aimed to observe the role of catalase in the survival strategy of filamentous fungi in extremely cold habitats and to identify the gene encoded catalase enzyme. Our results clearly showed that catalase is the main part of antioxidant enzyme defense in fungal cells against oxidative stress caused by low temperature exposure.

Low-grade endotoxemia and risk of recurrent thrombosis in primary antiphospholipid syndrome. The multicenter ATHERO-APS study

IntroductionLow-grade endotoxemia is associated with systemic inflammation, enhanced oxidative stress and cardiovascular events in different clinical settings, but its possible role as “second hit” in patients with primary antiphospholipid syndrome (PAPS) has never been investigated. PurposeTo evaluate the relationship between plasma lipopolysaccharide (LPS) levels, oxidative stress markers and risk of thrombosis in the prospective multicenter ATHERO-APS study. MethodsBaseline LPS, soluble NADPH-oxidase 2-derived peptide (sNOX-dp), H2O2 production, hydrogen peroxide breakdown activity (HBA), and nitric oxide (NO) bioavailability were compared in 97 PAPS, 16 non-thrombotic aPL carriers and 21 controls (CTRL) matched for age and sex. Correlations among laboratory variables were explored by Rho Spearman's correlation (rS). Cox-regression analysis was performed to assess the association between LPS and risk for a composite outcome of cardiovascular death, venous and arterial thromboembolism. ResultsIn the whole cohort (median age 51 years (IQR 43–60), 72 % female), PAPS demonstrated higher levels of LPS, sNOX-dp and H2O2 and lower levels of NO and HBA compared to non-thrombotic aPL carriers and CTRL. LPS levels were inversely correlated with HBA (rS: −0.295, p = 0.001) and NO (rS: −0.322, p < 0.001) and directly correlated with sNOX-dp (rS:0.469, p < 0.001) and H202 (rS:0.282, p < 0.001). PAPS showed higher levels of LPS, sNOX-dp and H2O2 and lower levels of NO and HBA compared to aPL carriers and CTRL. After a 4.7 years follow-up of, 11 composite outcomes were reported in PAPS (2.5 per 100 patient-years) while none was observed in aPL carriers. On Cox-regression analysis, patients with LPS above the median (>23.1 pg/ml) had a 5-fold increased risk of composite outcome compared to those with LPS below the median, after adjustment for sex, age, diabetes, and global antiphospholipid syndrome score. ConclusionLow-grade endotoxemia is associated with an increased oxidative stress and a higher risk of thrombosis in PAPS. Its prognostic value in carriers needs to be investigated in larger cohorts.

APE-1/Ref-1 Inhibition Blocks Malignant Pleural Mesothelioma Cell Proliferation and Migration: Crosstalk between Oxidative Stress and Epithelial Mesenchymal Transition (EMT) in Driving Carcinogenesis and Metastasis.

Malignant pleural mesothelioma (MPM) is an aggressive cancer associated with asbestos exposure. MPM pathogenesis has been related both to oxidative stress, evoked by and in response to asbestos fibers exposure, and epithelial mesenchymal transition (EMT), an event induced by oxidative stress itself and related to cancer proliferation and metastasis. Asbestos-related primary oxidative damage is counteracted in the lungs by various redox-sensitive factors, often hyperactivated in some cancers. Among these redox-sensitive factors, Apurinic-apyrimidinic endonuclease 1 (APE-1)/Redox effector factor 1 (Ref-1) has been demonstrated to be overexpressed in MPM and lung cancer, but the molecular mechanism has not yet been fully understood. Moreover, asbestos exposure has been associated with induced EMT events, via some EMT transcription factors, such as Twist, Zeb-1 and Snail-1, in possible crosstalk with oxidative stress and inflammation events. To demonstrate this hypothesis, we inhibited/silenced Ref-1 in MPM cells; as a consequence, both EMT (Twist, Zeb-1 and Snail-1) markers and cellular migration/proliferation were significantly inhibited. Taken as a whole, these results show, for the first time, crosstalk between oxidative stress and EMT in MPM carcinogenesis and invasiveness, thus improving the knowledge to better address a preventive and therapeutic approach against this aggressive cancer.

Oxidative Stress as a Regulatory Checkpoint in the Production of Antiphospholipid Autoantibodies: The Protective Role of NRF2 Pathway.

Oxidative stress is a well-known hallmark of Antiphospholipid Antibody Syndrome (APS), a systemic autoimmune disease characterized by arterial and venous thrombosis and/or pregnancy morbidity. Oxidative stress may affect various signaling pathways and biological processes, promoting dysfunctional immune responses and inflammation, inducing apoptosis, deregulating autophagy and impairing mitochondrial function. The chronic oxidative stress and the dysregulation of the immune system leads to the loss of tolerance, which drives autoantibody production and inflammation with the development of endothelial dysfunction. In particular, anti-phospholipid antibodies (aPL), which target phospholipids and/or phospholipid binding proteins, mainly β-glycoprotein I (β-GPI), play a functional role in the cell signal transduction pathway(s), thus contributing to oxidative stress and thrombotic events. An oxidation-antioxidant imbalance may be detected in the blood of patients with APS as a reflection of disease progression. This review focuses on functional evidence highlighting the role of oxidative stress in the initiation and progression of APS. The protective role of food supplements and Nuclear Factor Erythroid 2-Related Factor 2 (NRF2) activators in APS patients will be summarized to point out the potential of these therapeutic approaches to reduce APS-related clinical complications.