Oxidative Burden Research Articles

Oxidative stress as the bridge between dyslipidemia and peritoneal ultrafiltration failure: A bi-center cross-sectional cohort study

stress and dyslipidemia are common concerns in patients undergoing peritoneal dialysis (PD) and are associated with adverse clinical outcomes. However, the interplay between these factors and their impact on peritoneal ultrafiltration (UF) remains poorly understood.
 Methods: In this bi-center cross-sectional cohort study, we examined the relationships between dyslipidemia, oxidative stress, and peritoneal UF in patients undergoing PD. A comprehensive set of oxidative stress markers, lipid profiles, and clinical variables were assessed.
 Results. Among the 114 patients, aged 55 (48-65) years, with a dialysis vintage of 31 (14-50) months, 76 (66.7%) were diagnosed with dyslipidemia. Patients with dyslipidemia experienced significantly higher proportions of patients with peritoneal UF below 400 mL per day, suggesting ultrafiltration failure (UFF) (χ2 = 4.9, p = 0.02). An elevated D/P creatinine ratio was associated with higher levels of total cholesterol (r = 0.39, p = 0.0005), low-density lipoprotein cholesterol (r = 0.26, p = 0.02), triglycerides (r = 0.33, p = 0.005), and the atherogenic index of plasma (AIP) (r = 0.27, p = 0.01). UF rate displayed a positive correlation with high-density lipoprotein cholesterol (r = 0.31, p = 0.003) and a negative correlation with AIP (r = -0.33, p = 0.004). The ROC analysis revealed that an AIP value exceeding 4.3 could effectively predict UFF, with a sensitivity of 83.3% and a specificity of 73.4%
 Dyslipidemia was significantly associated with increased intensity of oxidative stress, with elevated malondialdehyde (MDA) (p = 0.0002), oxidative stress index (OSI) (p < 0.0001), and reduced antioxidant markers. UFF was also associated with higher oxidative stress, as indicated by increased MDA (p = 0.005) and OSI (p = 0.0009). Patients with both dyslipidemia and UFF exhibited the highest levels of oxidative stress (p < 0.0001). Taking potential confounders into account in the ANCOVA analysis, a significant interaction effect of dyslipidemia (F = 7.6, p = 0.007) and UF rate (F = 8.6, p = 0.004) on oxidative stress was observed.
 Conclusion. Dyslipidemia and UFF are independently associated with elevated oxidative stress in PD patients, and their coexistence exacerbates this oxidative burden. Understanding these relationships is crucial for developing interventions to improve clinical outcomes in this population. Targeted therapies addressing oxidative stress and dyslipidemia warrant further investigation.

Oxidative Stress in Type 2 Diabetes: Impacts from Pathogenesis to Lifestyle Modifications.

Oxidative stress is a critical factor in the pathogenesis and progression of diabetes and its associated complications. The imbalance between reactive oxygen species (ROS) production and the body's antioxidant defence mechanisms leads to cellular damage and dysfunction. In diabetes, chronic hyperglycaemia and mitochondrial dysfunction contribute to increased ROS production, further exacerbating oxidative stress. This oxidative burden adversely affects various aspects of diabetes, including impaired beta-cell function and insulin resistance, leading to disrupted glucose regulation. Additionally, oxidative stress-induced damage to blood vessels and impaired endothelial function contribute to the development of diabetic vascular complications such as retinopathy, nephropathy, and cardiovascular diseases. Moreover, organs and tissues throughout the body, including the kidneys, nerves, and eyes, are vulnerable to oxidative stress, resulting in diabetic nephropathy, neuropathy, and retinopathy. Strategies to mitigate oxidative stress in diabetes include antioxidant therapy, lifestyle modifications, and effective management of hyperglycaemia. However, further research is necessary to comprehensively understand the underlying mechanisms of oxidative stress in diabetes and to evaluate the efficacy of antioxidant interventions in preventing and treating diabetic complications. By addressing oxidative stress, it might be possible to alleviate the burden of diabetes and improve patient outcomes.

304-OR: Reduced VDAC1 Limits ROS Release to Restrain Oxidative Damage in Muscle of 3-Year-Old Nonhuman Primates with Early-Life Exposure to Maternal Western Diet or Obesity

Offspring from obese pregnancies have an elevated risk for childhood obesity and chronic metabolic diseases. Using a Japanese macaque model of early-life maternal Western-style diet (mWD) exposure, we previously observed decreased oxidative capacity and elevated markers of mitophagy in skeletal muscle of 3-yr-old offspring. We also found substantial reductions in VDAC1 content, the loss of which significantly correlated with decreased whole-muscle lipid peroxidation in mWD offspring. For this study, we isolated the impact of mWD from mWD-induced obesity by studying offspring from both lean (Ln, body fat <25%) or obese (Ob, body fat >30%) dams fed a WD or lean dams fed a control diet (CD) prior to and throughout pregnancy and lactation. All offspring were weaned to CD and offspring gastrocnemius was collected at 40 months of age. This design created three offspring groups: LnCD, LnWD and ObWD. In offspring muscle, VDAC1, but not VDAC2, was significantly decreased in LnWD, and was further reduced in ObWD. In contrast to whole-tissue, lipid peroxidation in a mitochondrial-enriched fraction was increased in offspring muscle from LnWD and ObWD groups. Markers of mtDNA damage were also elevated in ObWD muscle. Lastly, Sirt3 abundance, a master regulator of mitochondrial antioxidant defense, was reduced in muscle from both LnWD and ObWD. These data suggest that ROS are retained within the mitochondrial compartment due, in part, to VDAC1 suppression, resulting in an overall reduction in cellular oxidant burden. These findings elucidate a long-term adaptation to early life stress caused by mWD and obesity which limits cellular damage at the expense of mitochondrial function. Disclosure K.T.Greyslak: None. C.E.Mccurdy: None. Funding National Institutes of Health (R24DK090964); Eugene Evonuk Memorial Graduate Fellowship

Olive extract enriched with hydroxytyrosol improves cardiac and vascular function in patients with stable coronary artery disease: a double-blind, placebo-controlled trial

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): Olive Heart Operational Programme Competitiveness, Entrepreneurship and Innovation 2014–2020 (EPAnEK) Aims We investigated the effect of olive extract enriched with hydroxytyrosol, on vascular and myocardial function markers in patients with stable coronary artery disease (SCAD). Methods In a prospective, cross-over, double-blind, placebo-controlled, clinical trial, 30 patients with stable CAD were randomly assigned to an oral supplement containing olive oil extract enriched with hydroxytyrosol (OOHT) or placebo for one month and then were crossed over to the alternate treatment (placebo or OOHT for one more month). We measured a) perfused boundary region (PBR) of the sublingual arterial microvessels (increased PBR indicates reduced endothelial glycocalyx thickness), b) flow-mediated dilation (FMD), c) Coronary Flow Reserve (CFR) and markers of LV diastolic function by Doppler echocardiography d) Pulse Wave Velocity (PWV) e) oxidative/nitrosative stress and inflammatory biomarkers and blood lipids at baseline and after one month treatment. Results Treatment with OOHT improved PBR, FMD, CFR and PWV compared to baseline (1.81±0.35 vs 1.77±0.40 μm p = 0.04 3.71±2.12 vs 6.51±2.31%, p<0.001;2.37±0.40 vs 2.45±0.41, p = 0.030 and 11.03±1.81 vs 11.78±2.34 m/sec, p = 0.002), while there was no effect after placebo (p>0.05). Compared to baseline, treatment with OOHT reduced malondialdehyde (MDA) a marker of lipid peroxidation (2.10±1.37 vs 1.69±0.83 mmol/lt, p = 0.045), oxidized LDL, triglycerides, PCSK9 and CRP blood levels (p<0.05) in contrast to placebo. There was a parallel improvement of E’ of the mitral annulus and deceleration time of the E wave of mitral inflow after OOHT (p<0.05) but not after placebo. Conclusions Olive extract enriched with hydroxytyrosol improves endothelial and arterial function likely by reducing oxidative and inflammatory burden leading to improved LV diastolic function after one month of treatment in patients with stable CAD.

Oxidative balance score is inversely associated with the incidence of non-alcoholic fatty liver disease

The contribution of the balance between overall oxidative stress and antioxidant status in non-alcoholic fatty liver disease (NAFLD) is unclear. The oxidative balance score (OBS) comprises dietary and lifestyle pro- and antioxidant components that indicate the overall oxidative stress burden. We investigated the association between OBS and the incidence of NAFLD in middle-aged and older Korean adults. Among the 10,030 participants of the Korean Genome and Epidemiology Study_Ansan and Ansung cohort, 5065 without NAFLD at baseline were selected for secondary analysis. OBS was categorized into quartiles. Multiple Cox proportional hazard regression analyses were performed to estimate the hazard ratio (HR) and 95% confidence interval (CI) for NAFLD incidence by sex-specific OBS quartile groups after adjusting for confounders. During the follow-up period (median 13.4 years), 913 (43.2%) men and 1288 (43.9%) women were newly diagnosed with NAFLD. Compared with that of the lowest quartile (Q1) group, the adjusted HR (95% CI) for NAFLD incidence in Q2, Q3, and Q4 groups was 0.85 (0.71-1.00), 0.65 (0.54-0.78), and 0.50 (0.40-0.62) in men, and 0.85 (0.73-0.99), 0.66 (0.56-0.77), and 0.48 (0.40-0.59) in women, respectively, and for NAFLD incidence, per incremental change in OBS, was 0.90 (0.87-0.92) in men and 0.88 (0.86-0.90) in women. A higher OBS was significantly associated with a lower risk for NAFLD incidence. Maintaining a healthy lifestyle and an antioxidant-rich diet is a potentially viable strategy for preventing NAFLD.

Portulaca oleracea L. (purslane) improves the anti-inflammatory, antioxidant and autophagic actions of metformin in the hippocampus of diabetic demented rats

Great body of evidence links cognitive decline to diabetes/insulin resistance. In this study the effect of Portulaca oleracea (PUR) (100 mg/kg), Metformin (MET) (200 mg/kg), a first line diabetes mellitus type 2 therapy, and their combination on cognitive function and hippocampal markers in diabetic rats were assessed. Male rats were injected with streptozotocin (30 mg/kg on two successive weeks) followed by 4 weeks of treatment. Possible antioxidant, anti-inflammatory, and autophagy enhancing mechanisms of these drugs were investigated in the hippocampal tissue using spectrophotometry, ELISA, and western blotting. Diabetic rats suffered significant cognitive impairment in Morris's water maze, hippocampal TBARS elevation, GSH depletion, and SOD upregulation. In addition, diabetes promoted the secretion of hippocampal inflammatory cytokines, TNF-α and IL-1β, and depleted anti-inflammatory cytokines as IL-10. Such detrimental changes were reversed by MET and/or PUR. Notably, AMPK was upregulated by diabetes, then restored to normal by MET and/or PUR. The pattern of change in AMPK expression was concomitant with changes in oxidative and inflammatory burden. Hence, AMPK is believed to be a key mediator in most of the measured pre-AD markers in this study. However, from our results, PUR is believed to have non-AMPK dependent actions as well.In conclusion, antidiabetic agents as metformin and purslane extract proved to be invaluable in addressing the cognitive decline and hippocampal changes that arise as a complication of diabetes. They mainly acted through AMPK pathway; however, their usefulness was not limited to AMPK pathways since their combination was suggested to have a different mechanism.

Assessing the chemical composition, potential toxicity and cancer risk of airborne fine particulate matter (PM2.5) near a petrochemical industrial area

In the vicinity of a petrochemical industrial region in São Paulo, Brazil, PM2.5-bound organic carbon (OC), elemental carbon (EC), polycyclic aromatic hydrocarbons (PAHs), nitro-PAHs, oxy-PAHs, hopanes, and inorganic species were evaluated. Oxidative potential (OP), burden (OB), and Alivibrio fischeri bioluminescence inhibition (AFBIA) assays were conducted to determine the potential health effects of exposure to these compounds. The PM2.5 mean concentration was 32.0 ± 18.2 µg m−3, and benzo (a)pyrene was found to exceed recommended levels by at least four times. Secondary sources and vehicular emissions were indicated by nitro-PAHs, oxy-PAHs, and inorganic species. The OP and OB results revealed that secondary compounds favored antioxidant depletion. The AFBIA results showed that 64 % of the samples were toxic. These findings emphasize the need to reduce the exposure risk and take measures to protect human health.

CARD2: Plasma Homocysteine and Oxidative Stress Markers May Predict the Stress Burden of Human Hearts Donated After Circulatory Death

Background: Initial result of heart transplantation using donation after circulatory death (DCD) heart with warm ischemic time (WIT) less than 30 minutes was encouraging. However, little is known about how donor respond to WIT systemically and its impact on the heart with subsequent cold storage as used in normothermic regional perfusion(NRP) on the DCD hearts. Since elevated homocysteine (Hcy) and oxidative stress burden in cardiovascular system have been associated with ischemia, we investigated if circulating Hcy, oxidative stress and antioxidant were elevated in DCD blood and myocardium and if there is temporal relationship with the WIT and subsequent cold storage. Methods: We studied 12 human DCD hearts for research (WIT range:20-110 min). They were assigned to 3 groups of WIT [20 (n=4), 40 (n=5), ≥60 (n=3) min.]. Two time-point donor blood samples were collected from each donor at the baseline (prior to or at extubation) and at the cross-clamp. All hearts received del Nido cardioplegia before they were placed at cold storage for 6 hours. Left ventricular (LV) biopsies were performed at hour 0,2,4 and 6. Circulating Hcy, oxidative stress (oxidized low-density lipoprotein: OxLDL, malondialdehyde: MDA) and total antioxidant in blood were quantified. The MDA and GPx activity (glutathione peroxidase: antioxidant) were quantified in cardiac biopsies. Results: Change in plasma Hcy (Fig.1A), oxidative stress (Fig.1B,C) and antioxidant (Fig.1D) found to be comparable between the 3 groups at baseline; while significant differences were noticed in samples at cross-clamping; especially in DCD≥60 groups. The WIT found to be positively correlated Hcy and oxidative stress at cross-clamping; and negatively correlated with antioxidant (p<0.05,Table:1). The myocardial oxidative stress (MDA) found to be minimal at baseline (DCD20 and 40), and slightly elevated at 2 hrs. and maintained at similar levels at 4 and 6 hrs. of cold storage (Fig.1E); while a preexisting high oxidative stress at baseline in DCD≥60, an exponential increase during the cold storage indicating severity of stress burden. Temporal decrease in cardiac antioxidant (GPx) found to be more pronounced in DCD≥60 group, while the rates of change are comparable in DCD:20 and 40 groups (Fig.1F). The change of blood markers was found to be correlated with change of myocardial markers(Table:1). Conclusions: Systemic warm ischemia promoted hyperhomocystenemia and increased oxidative stress and might be used as initial screening biomarkers for the stress burden on the donor hearts. The correlation between blood and myocardial markers suggested the systemic markers can potentially be used in predicting stress burden of donor hearts. The duration of cold storage was related to progressive increase in myocardial oxidative stress and diminished antioxidant status. We recommend rejecting DCD hearts with WIT≥60 minutes, as both the blood and tissue data indicating maximum oxidative stress burden in this group.

The Role of Retinal Pigment Epithelial Cells in Age-Related Macular Degeneration: Phagocytosis and Autophagy.

Age-related macular degeneration (AMD) causes vision loss in the elderly population. Dry AMD leads to the formation of Drusen, while wet AMD is characterized by cell proliferation and choroidal angiogenesis. The retinal pigment epithelium (RPE) plays a key role in AMD pathogenesis. In particular, helioreceptor renewal depends on outer segment phagocytosis of RPE cells, while RPE autophagy can protect cells from oxidative stress damage. However, when the oxidative stress burden is too high and homeostasis is disturbed, the phagocytosis and autophagy functions of RPE become damaged, leading to AMD development and progression. Hence, characterizing the roles of RPE cell phagocytosis and autophagy in the pathogenesis of AMD can inform the development of potential therapeutic targets to prevent irreversible RPE and photoreceptor cell death, thus protecting against AMD.

Pachymic acid modulates sirtuin 6 activity to alleviate lipid metabolism disorders.

Pachymic acid (Pac), a major bioactive constituent of Poria cocos, is an antioxidant that inhibits triglyceride (TG) accumulation. To the best of our knowledge, the present study investigated for the first time whether Pac activated sirtuin 6 (SIRT6) signaling to alleviate oleic acid (OA)-palmitic acid (PA)-induced lipid metabolism disorders in mouse primary hepatocytes (MPHs). In the present study, MPHs challenged with Pac were used to test the effects of Pac on intracellular lipid metabolism. Molecular docking studies were performed to explore the potential targets of Pac in defending against lipid deposition. MPHs isolated from liver-specific SIRT6-deficient mice were subjected to OA + PA incubation and treated with Pac to determine the function and detailed mechanism. It was revealed that Pac activated SIRT6 by increasing its expression and deacetylase activity. Pa prevented OA + PA-induced lipid deposition in MPHs in a dose-dependent manner. Pac (50 µM) administration significantly reduced TG accumulation and increased fatty acid oxidation rate in OA + PA-incubated MPHs. Meanwhile, as per the results of molecular docking and relative mRNA levels, Pac activated SIRT6 and increased SIRT6 deacetylation levels. Furthermore, SIRT6 deletions in MPHs abolished the protective effects of Pac against OA + PA-induced hepatocyte lipid metabolism disorders. The present study demonstrated that Pac alleviates OA + PA-induced hepatocyte lipid metabolism disorders by activating SIRT6 signaling. Overall, SIRT6 signaling increases oxidative stress burden and promotes hepatocyte lipolysis.

Application of an Integrative Drug Safety Model for Detection of Adverse Drug Events Associated With Inhibition of Glutathione Peroxidase 1 in Chronic Obstructive Pulmonary Disease

BackgroundChronic Obstructive Pulmonary Disease is characterised by declining lung function and a greater oxidative stress burden due to reduced activity of antioxidant enzymes such as Glutathione Peroxidase 1.ObjectivesThe extent to which drugs may contribute to this compromised activity is largely unknown. An integrative drug safety model explores inhibition of Glutathione Peroxidase 1 by drugs and their association with chronic obstructive pulmonary disease adverse drug events.MethodsIn silico molecular modelling approaches were utilised to predict the interactions that drugs have within the active site of Glutathione Peroxidase 1 in both human and bovine models. Similarities of chemical features between approved drugs and the known inhibitor tiopronin were also investigated. Subsequently the Food and Drug Administration Adverse Event System was searched to uncover adverse drug event signals associated with chronic obstructive pulmonary disease.ResultsStatistical and molecular modelling analyses confirmed that the use of several registered drugs, including acetylsalicylic acid and atenolol may be associated with inhibition of Glutathione Peroxidase 1 and chronic obstructive pulmonary disease.ConclusionThe integration of molecular modelling and pharmacoepidemological data has the potential to advance drug safety science. Ongoing review of medication use and further pharmacoepidemiological and biological analyses are warranted to ensure appropriate use is recommended.Graphical

Angelica sinensis polysaccharides alleviate the oxidative burden on hematopoietic cells by restoring 5-fluorouracil-induced oxidative damage in perivascular mesenchymal progenitor cells

Context 5-Fluorouracil (5-FU)-injured stromal cells may cause chronic bone marrow suppression; however, the underlying mechanism remains unclear. Angelica sinensis polysaccharide (ASP), the main biologically active ingredient of the Chinese herb, Angelica sinensis (Oliv.) Diels (Apiaceae), may enrich the blood and promote antioxidation. Objective This study investigated the protective antioxidative effects of ASP on perivascular mesenchymal progenitors (PMPs) and their interactions with hematopoietic cells. Materials and methods PMPs were dissociated from C57BL/6 mouse femur and tibia and were subsequently divided into the control, ASP (0.1 g/L), 5-FU (0.025 g/L), and 5-FU + ASP (pre-treatment with 0.1 g/L ASP for 6 h, together with 0.025 g/L 5-FU) then cultured for 48 h. Hematopoietic cells were co-cultured on these feeder layers for 24 h. Cell proliferation, senescence, apoptosis, and oxidative indices were detected, along with stromal osteogenic and adipogenic differentiation potentials. Intercellular and intracellular signaling was analyzed by real-time quantitative reverse transcription polymerase chain reaction and Western blotting. Results ASP ameliorated the reactive oxygen species production/scavenge balance in PMPs; improved osteogenic differentiation; increased SCF, CXCL12, VLA-4/VCAM-1, ICAM-1/LFA1, and TPO/MPL, Ang-1/Tie-2 gene expression. Further, the ASP-treated feeder layer alleviated hematopoietic cells senescence (from 21.9 ± 1.47 to 12.1 ± 1.13); decreased P53, P21, p-GSK-3β, β-catenin and cyclin-D1 protein expression, and increased glycogen synthase kinase (GSK)-3β protein expression in co-cultured hematopoietic cells. Discussion and conclusions ASP delayed oxidative stress-induced premature senescence of 5-FU-treated feeder co-cultured hematopoietic cells via down-regulation of overactivated Wnt/β-catenin signaling. These findings provide a new strategy for alleviating myelosuppressive stress.

Epigenetic and non-epigenetic mechanisms in the accelerated cellular aging in late-onset Alzheimer’s disease

Late-onset Alzheimer’s disease (LOAD) is the most common form of Alzheimer’s disease (AD) and its risk increases exponentially with aging. The incidence of LOAD is reported to increase from 1 in every 1,000 people aged 37 to 65 in every 100 people aged 80 years and older. LOAD is extensively associated with aging and cognition decline. Several risk factors, including lifestyle choices, environmental factors, and medical ailments, affect cellular stress. The cellular stress can bring upon epigenetic alterations that affect cellular aging making the individual more susceptible to LOAD development. In due course the cellular stress resulting into epigenetic deregulation, oxidative burden, and genomic mutations leads to increased disease risk. Role of epigenetic and non-epigenetic mechanisms in accelerated cellular aging that are reported to increase the risk of LOAD development are summarized in this review. The underlying biological mechanism of cellular aging and the risk factors that could predispose cellular aging and LOAD development are also discussed in the upcoming sections.

NADPH Oxidase Subunit CYBB Confers Chemotherapy and Ferroptosis Resistance in Mesenchymal Glioblastoma via Nrf2/SOD2 Modulation.

Glioblastoma multiforme (GBM) is a highly heterogeneous disease with a mesenchymal subtype tending to exhibit more aggressive and multitherapy-resistant features. Glioblastoma stem-cells derived from mesenchymal cells are reliant on iron supply, accumulated with high reactive oxygen species (ROS), and susceptible to ferroptosis. Temozolomide (TMZ) treatment is the mainstay drug for GBM despite the rapid development of resistance in mesenchymal GBM. The main interconnection between mesenchymal features, TMZ resistance, and ferroptosis are poorly understood. Herein, we demonstrated that a subunit of NADPH oxidase, CYBB, orchestrated mesenchymal shift and promoted TMZ resistance by modulating the anti-ferroptosis circuitry Nrf2/SOD2 axis. Public transcriptomic data re-analysis found that CYBB and SOD2 were highly upregulated in the mesenchymal subtype of GBM. Accordingly, our GBM cohort confirmed a high expression of CYBB in the GBM tumor and was associated with mesenchymal features and poor clinical outcome. An in vitro study demonstrated that TMZ-resistant GBM cells displayed mesenchymal and stemness features while remaining resilient to erastin-mediated ferroptosis by activating the CYBB/Nrf2/SOD2 axis. The CYBB maintained a high ROS state to sustain the mesenchymal phenotype, TMZ resistance, and reduced erastin sensitivity. Mechanistically, CYBB interacted with Nrf2 and consequently regulated SOD2 transcription. Compensatory antioxidant SOD2 essentially protected against the deleterious effect of high ROS while attenuating ferroptosis in TMZ-resistant cells. An animal study highlighted the protective role of SOD2 to mitigate erastin-triggered ferroptosis and tolerate oxidative stress burden in mice harboring TMZ-resistant GBM cell xenografts. Therefore, CYBB captured ferroptosis resilience in mesenchymal GBM. The downstream compensatory activity of CYBB via the Nrf2/SOD2 axis is exploitable through erastin-induced ferroptosis to overcome TMZ resistance.

A sustainable bioeconomy approach for improved biodiesel production using photocatalytic GO@CN assisted cultivation of Chlorosarcinopsis sp. MAS04

Low biomass yield and lipid production limits the development of microalgae-derived biodiesel on a wide scale. However, the use of photo-responsive nanomaterials as a substrate for microalgae can resolve these issues and enhance its economic viability. The current investigation highlights the potential of graphene oxide; graphitic carbon nitride (GO@CN) as a photocatalytic material for Chlorosarcinopsis sp. MAS04. A suite of characterization techniques including Scanning electron microscope (SEM), X-ray powder diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and Zeta potential was used to perceive the structural, morphological, and stability insights of the synthesized nanocomposite. Cytotoxicity assay for 96 h was performed for testing microalgal viability. Subsequently, microalgae cultures were supplemented with 0–200 mg L−1 of synthesized nanocomposite for 30 days. The intracellular reactive oxygen species (ROS) concentration was estimated to determine the oxidative stress burden. The incurred cellular lipids were processed into fatty acid methyl esters (FAMEs) possessing suitable biodiesel characteristics. The 50 mg L−1 of the optimal supplement of GO@CN for microalgae cultivation results in the highest biomass and lipid production of 3.825 g L−1 and 38.5% respectively, that is a 1.5-fold increase in biomass and nearly a 1.9-fold rise in lipid content, compared to the control. Additionally, a cost-benefit analysis of the developed process inferred a 350% increase in FAME yield at an expense of 0.15 g/INR more than the cost estimated for the control. Thus, this amalgamation of nano-algal science could be a prospective approach for augmenting microalgae-based biodiesel as a sustainable bioeconomy.

Association of hydroxytyrosol enriched olive oil with vascular function in chronic coronary disease.

Hydroxytyrosol reduces Low-Density lipoprotein oxidation, contributing to prevention of atherosclerosis progression. In a prospective, cross-over, double-blind, placebo-controlled trial, 30 chronic coronary artery syndrome (CCAS) patients were randomized to 4 capsules/day, containing 412.5 mg olive oil with 2.5 mg hydroxytyrosol (OOHT) each one or placebo for one month and then were crossed-over to the alternate treatment (placebo or OOHT). We measured a) perfused boundary region (PBR) of the sublingual arterial microvessels (increased PBR indicates reduced glycocalyx thickness), b) flow-mediated dilation (FMD), c) Coronary Flow Reserve (CFR) and markers of LV diastolic function by Doppler echocardiography, d) Pulse Wave Velocity (PWV), e) oxidative stress, inflammatory biomarkers and blood lipids at baseline and after treatment. Treatment with OOHT improved PBR, FMD, CFR and PWV compared to baseline (1.8±0.3vs1.7±0.4 μm, p=0.040, 3.7±2.1vs6.5±2.3%, p<0.001, 2.3±0.4vs2.5±0.4, p=0.030 and 11.1±1.8vs11.8±2.3 m/sec, p=0.002 while there was no effect after placebo (p=NS). No effect of OOHT treatment was observed on blood pressure. There was a parallel improvement of E' of the mitral annulus and deceleration time of the E wave of mitral inflow after OOHT (p<0.05) but not after placebo. Compared to baseline, treatment with OOHT reduced malondialdehyde, a marker of lipid peroxidation, oxidized LDL, triglycerides, PCSK9 and CRP blood levels (p<0.05) in contrast to placebo. Hydroxytyrosol-enriched olive oil may have beneficial effects on endothelial, arterial and LV diastolic function likely by reducing oxidative and inflammatory burden in CCAS, though further studies are needed to confirm this mechanism.

Organic ultraviolet filter mixture promotes bleaching of reef corals upon the threat of elevated seawater temperature

Global reef degradation is a critical environmental health issue that has triggered intensive research on ocean warming, but the implications of emerging contaminants in coral habitats are largely overlooked. Laboratory experiments assessing organic ultraviolet (UV) filter exposure have shown that these chemicals negatively affect coral health; their ubiquitous occurrence in association with ocean warming may pose great challenges to coral health. We investigated both short- (10-day) and long-term (60-day) single and co-exposures of coral nubbins to environmentally relevant organic UV filter mixtures (200 ng/L of 12 compounds) and elevated water temperatures (30 °C) to investigate their effects and potential mechanisms of action. The initial 10-day exposure of Seriatopora caliendrum resulted in bleaching only under co-exposure conditions (compounds + temperature). The 60-day mesocosm study entailed the same exposure settings with nubbins of three species (S. caliendrum, Pocillopora acuta and Montipora aequituberculata). Bleaching (37.5 %) and mortality (12.5 %) of S. caliendrum were observed under UV filter mixture exposure. In the co-exposure treatment, 100 % S. caliendrum and P. acuta bleached associating with 100 % and 50 % mortality, respectively, and significant increase of catalase activities in P. acuta and M. aequituberculata nubbins were found. Biochemical and molecular analyses indicated significant alteration of oxidative stress and metabolic enzymes. The results suggest that upon the adverse effects of thermal stress, organic UV filter mixture at environmental concentrations can cause bleaching in corals by inducing a significant oxidative stress and detoxification burden, suggesting that emerging contaminants may play a unique role in global reef degradation.

The interplay of oncogenic signaling, oxidative stress and ferroptosis in cancer.

Oncogene-induced hyper-proliferation in cancer cells is accompanied by the onset of different stresses, including DNA-replication stress, metabolic stress and oxidative stress. Excessive accumulation of reactive oxygen species (ROS) plays a pivotal and contradictory role in tumor progression. ROS dictates a multitude of cell signaling pathways to facilitate the malignant transformation of tumor cells. In the meantime, oxidative burden in tumor cells mandates reinforcing antioxidant capacity to mitigate detrimental damages. The addiction to oxidative stress and increased iron demands in cancer cells also impinges on the sensitivity of ferroptosis. Targeting redox homeostasis and ferroptosis to overcome drug resistance in cancer treatment has become an attractive research topic. However, the roles of oncogenic signaling in redox regulation and ferroptosis have not been comprehensively discussed. In this review, we summarize current knowledge regarding the interplay between redox regulation and ferroptosis in the context of cancer biology. We emphasize the implication of oncogenic signaling in redox homeostasis and ferroptosis regulation. We also provide an overview of strategies targeting oxidative stress and ferroptosis in cancer treatment.

Do Antioxidants Extend Longevity in Invertebrate and Vertebrate Animals?

In the 1950’s Denham Harman proposed the Free Radical Theory of Aging whereby species lifespan and individual longevities are the consequence of free radical driven damage to biomolecules. This led to decades of research to ascertain the effect of altered antioxidant defense systems on aging and mortality in an array of species using reverse genetics and dietary manipulation. Within invertebrates, the data generally support the Free Radical Theory in that overexpression of antioxidant enzymes or dietary supplementation with antioxidant compounds increases longevity and resistance to oxidative damage. Likewise, genetic knockdown of antioxidant defenses generally shortens longevity within invertebrates. On the other hand, for endothermic vertebrates (i.e., birds and mammals) the results have been equivocal. Downregulation of antioxidant enzymes typically results in an increased oxidative burden, but without an appreciable effect on longevity, while dietary supplementation with antioxidants has little-to-no effect, at least at the concentrations used. Upregulation of antioxidant enzyme genes also fails to increase longevity in vertebrates most of the time. Interestingly, manipulating antioxidant defenses in fishes increases longevity in conjunction with reduced oxidative damage akin to what is seen in invertebrates. Since invertebrates and fishes are both exothermic this raises the possibility that the evolution of endothermy interferes with the ability of antioxidants to slow the aging process.

Caffeine improves memory and cognition via modulating neural progenitor cell survival and decreasing oxidative stress in Alzheimer's rat model.

Caffeine possesses potent antioxidant, anti-inflammatory and anti-apoptotic activities against a variety of neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD). The goal of this study was to investigate the protective role of a psychoactive substance like caffeine on hippocampal neurogenesis and memory functions in streptozotocin (STZ)-induced neurodegeneration in rats. Caffeine is a natural CNS stimulant, belonging to the methylxanthine class, and is a widely consumed psychoactive substance. It is reported to abate the risk of various abnormalities that are cardiovascular system (CVS) related, cancer related, or due to metabolism dysregulation. Short-term caffeine exposure has been widely evaluated, but its chronic exposure is less explored and pursued. Several studies suggest a devastating role of caffeine in neurodegenerative disorders. However, the protective role of caffeine on neurodegeneration is still unclear. Here, we examined the effects of chronic caffeine administration on hippocampal neurogenesis in intracerebroventricular STZ injection induced memory dysfunction in rats. The chronic effect of caffeine on proliferation and neuronal fate determination of hippocampal neurons was evaluated by co-labeling of neurons by thymidine analogue BrdU that labels new born cells, DCX (a marker for immature neurons) and NeuN that labels mature neurons. STZ (1 mg/kg, 2 μl) was injected stereotaxically into the lateral ventricles (intracerebroventricular injection) once on day 1, followed by chronic treatment with caffeine (10 mg/kg, i.p) and donepezil (5 mg/kg, i.p.). Protective effect of caffeine on cognitive impairment and adult hippocampal neurogenesis was evaluated. Our findings show decreased oxidative stress burden and amyloid burden following caffeine administration in STZ lesioned SD rats. Further, double immunolabeling with bromodeoxyuridine+/doublecortin+ (BrdU+/DCX+) and bromodeoxyuridine+/ neuronal nuclei+ (BrdU+/NeuN+) has indicated that caffeine improved neuronal stem cell proliferation and long term survival in STZ lesioned rats. Our findings support the neurogenic potential of caffeine in STZ induced neurodegeneration.