Low Levels Of Oxidative Stress Research Articles

Oxidative Homeostasis in Follicular Fluid and Embryo Quality-A Pilot Study.

The objective of this study was to measure the different redox biomarker levels within the follicular fluid (FF) and evaluate correlations with embryo quality using the one follicle-one oocyte/embryo approach. The prospective study included 54 women (average age 34.6 ± 3.0 years). Out of the 235 mature metaphase II cells that underwent intracytoplasmic sperm injection, fertilization was achieved in 177 cells, producing 92 Grade I embryos, 26 Grade II embryos, 39 Grade III embryos, and 20 Grade IV embryos. The activities of antioxidant enzymes, superoxide dismutase, glutathione peroxidase, and glutathione transferase were significantly higher in the group consisting of lower-quality (Grades II-IV) embryos in comparison with top-quality (Grade I) embryos (p = 0.011; p = 0.021; p = 0.008, respectively). The concentration of oxidative stress markers, malondialdehyde, 8-hydroxy-2'-deoxyguanosine, and thiol groups was significantly increased in the group with lower-quality embryos (Grades II-IV) compared to top-quality embryos (0.027; 0.018; 0.021, respectively). Furthermore, a significant positive correlation between each oxidative marker and the activities of antioxidant enzymes was observed (p < 0.001). According to our findings, the best embryos and, consequently, better in vitro fertilization outcomes are linked to low levels of oxidative stress and low antioxidant enzyme activity.

IL20RA Is the Key Factor Contributing to the Stronger Antioxidant Capacity of Rongchang Pig Sertoli Cells

Variations in disease resistance among pig breeds have been extensively documented, with Sertoli cells (SCs) playing a pivotal role in spermatogenesis. Infections can induce oxidative stress, which can lead to damage to these cells. This study aimed to compare the levels of oxidative stress in SCs from Rongchang and Landrace pig breeds following LPS challenge. SCs were isolated, cultured, and stimulated with LPS to assess cell viability and markers of oxidative stress. Cell viability was evaluated along with oxidative stress markers such as reactive oxygen species (ROS), mitochondrial superoxide, malondialdehyde, and antioxidant enzymes. Mitochondrial function was assessed using JC-1 and Calcein AM probes. Transcriptomic analysis identified differentially expressed genes (DEGs), while ingenuity pathway analysis (IPA) explored enriched pathways. IL20RA, identified through transcriptomics, was validated using the siRNA knockdown technique. The results showed that Rongchang SCs exhibited lower levels of oxidative stress compared to Landrace SCs along with higher activity of antioxidant enzymes. IL20RA emerged as a key regulator since its knockdown affected mitochondrial superoxide production and catalase secretion. The findings suggest that Rongchang SCs possess superior antioxidant capacity, possibly due to the IL20RA-mediated protection of mitochondria, thereby providing insights into breed-specific resistance against oxidative stress and highlighting the role of IL20RA in maintaining stem cell function.

Association between the oxidative balance score with metabolic syndrome traits in US adults

ObjectiveTo explore the association between the Oxidative Balance Score (OBS), which represents the balance of multiple oxidative stress-related dietary and lifestyle exposures, and the risk of metabolic syndrome (MetS).MethodsA population-based cross-sectional study design was adopted and 16,850 participants in NHANES database were included in the statistics analysis stage. The OBS was constructed by combining information from 20 a priori selected pro- and antioxidant factors. Weighted logistic regression and restricted cubic splines (RCS) were used to estimate the association between OBS and MetS.ResultsParticipants in the highest OBS quartile, indicating low oxidative stress (OS) levels, exhibited a significantly lower risk of MetS (odds Ratio [OR] = 0.55, 95% confidence Interval [CI]: 0.47–0.64) compared to the lowest quartile. Specifically, higher OBS was inversely associated with abdominal obesity (OR = 0.61, 95% CI: 0.54–0.69), hypertension (OR = 0.69, 95% CI: 0.58–0.83), elevated triglycerides (OR = 0.68, 95% CI: 0.57–0.82), low high-density lipoprotein cholesterol (HDL-C) levels (OR = 0.60, 95% CI: 0.50–0.70) and fasting blood glucose (FBG) levels (OR = 0.74, 95% CI: 0.62–0.88). The observed inverse association between OBS and hypertension or FBG levels appeared to primarily influenced by BMI. The association between dietary OBS intervals and elevated FBG levels was not statistically significant in men, whereas the risk was lower by 25% in women.ConclusionsA higher OBS, representing a balance of multiple oxidative stress-related dietary and lifestyle exposures, is associated with a lower risk of MetS. Therefore, adhering to an antioxidant diet and lifestyle may help prevent the occurrence of metabolic disorders.

Unraveling Neurotoxicity Discrepancies: Comparative In vitro and In vivo Analysis of Colistin and Polymyxin B and the Underlying Mechanisms.

Polymyxins, including colistin and polymyxin B, are the final resort against Gram-negative bacterial infections. However, its clinical application is restricted due to concerns related to neurotoxicity. Despite the similar antibacterial spectrum and mode of action shared between colistin and polymyxin B, there is still a lack of definitive evidence to support the idea that their neurotoxicity profiles are identical. To comprehensively compare the neurotoxicity between colistin and polymyxin B both in vivo and in vitro and establish a theoretical foundation to guide the rational use of polymyxins within clinical settings. in vitro experiments simulated nerve damage by exposing N2a and RSC96 cells to colistin and polymyxin B. The evaluation of nerve injury included assessments of cell viability and apoptosis. To discern the variance in the mechanisms of nerve injury between colistin and polymyxin B, oxidative stress levels were examined, such as SOD, CAT, GSH, and malondialdehyde (MDA). In in vivo experiments, a rat nerve injury model was created by intraventricular injections of colistin and polymyxin B, respectively. The impact of these drugs on brain injury in rats, particularly within the hippocampus and medulla oblongata, was measured using HE and Nissl staining. The potential influence of polymyxins on the ferroptosis pathway was evaluated by assessing LPO and Fe2+ levels and the degree of mitochondrial impairment. At equivalent doses, colistin demonstrated a reduced level of neurotoxicity compared to polymyxin B, both in vitro and in vivo. in vitro experiments revealed greater cell viability and a lower apoptosis rate after colistin treatment than after polymyxin B treatment. This variance in outcomes could be attributed to the comparatively lower levels of oxidative stress associated with colistin administration.In a rat model, nerve injury resulted in observable damage to both the hippocampus and the medulla oblongata. A comprehensive assessment of the extent of damage in the CA1 to CA4 regions of the hippocampus, and the solitary tract nucleus of the medulla oblongata underscored that the neurotoxic effects of colistin remained milder compared to those elicited by polymyxin B. Even when evaluated at equivalent multiples of clinically recommended doses, colistin exhibited lower neurotoxicity in vivo than polymyxin B. For the first time, this study demonstrated the role of ferroptosis in polymyxin B-induced nerve damage. The activation levels observed within the ferroptosis pathway due to polymyxin B exceeded those triggered by colistin. Colistin exhibited a marked reduction in neurotoxicity compared to polymyxin B, evident in both the equivalent and clinically recommended doses. These findings suggest that, from the perspective of neurotoxicity, colistin presents a more favorable option for clinical use.

Protective properties of milk-derived peptide QEPV in attenuating oxidative stress through AMPK/PPARα signaling pathways

Peptides derived from fermented milk have demonstrated diverse bioactivities. In this study, we investigated the protective effects of Gln-Glu-Pro-Val (QEPV) against hydrogen peroxide (H2O2) induced oxidative stress in RAW 264.7 cells and further evaluated its potential in Drosophila melanogaster (D. melanogaster). Pre-incubation with QEPV in vitro dose-dependently promoted cell viability, suppressed oxidative damage, and increased antioxidant enzyme activities in a low-level oxidative stress model. QEPV remarkably extended lifespan under the low-level oxidative stress, validating its practical applicability. These effects were attributed to the upregulation of 5′ adenosine monophosphate-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor alpha (PPARα) signaling pathways, as revealed by label-free proteomic analysis. To confirm the roles of these two signaling pathways, antagonists of AMPK (Dorsomorphin) and PPARα (GW6471) were applied in vitro and in vivo. The protective effects of QEPV were reversed by both antagonists. Overall, QEPV exhibits protective properties by selectively upregulating the AMPK and PPARα signaling pathways, indicating its potential application as an antioxidant food ingredient.

Pasture-finishing of cattle in Western U.S. rangelands improves markers of animal metabolic health and nutritional compounds in beef

As environmental and health concerns of beef production and consumption mount, there is growing interest in agroecological production methods, including finishing beef cattle on pastures with phytochemically diverse grasses, forbs, and/or shrubs. The goal of this metabolomics, lipidomics, and fatty acid methyl ester profiling study was to compare meat (pectoralis profundus) of Black Angus cattle from two commercial US beef finishing systems (pasture-finished on Western U.S. rangeland; n = 18 and grain-finished in a Midwest U.S. feedlot; n = 18). A total of 907 out of 1575 compounds differed in abundance between pasture-finished and grain-finished beef samples (all, false discovery rate adjusted P < 0.05). Pasture-finished beef contained higher levels of phenolic antioxidants (2.6-fold), alpha-tocopherol (3.1-fold), nicotinate/vitamin B3 (9.4-fold), choline (1.2-fold), myo-inositol (1.8-fold), and omega-3 fatty acids (4.1-fold). Grain-finished beef contained higher levels of gamma-tocopherol (14.6-fold), nicotinamide/vitamin B3 (1.5-fold), pantothenate/vitamin B5 (1.3-fold), and pyridoxine/vitamin B6 (1.3-fold); indicating that feeding some grain (by-products) could be beneficial to increase levels of certain B-vitamins. Pasture-finished beef samples also displayed lower levels of oxidative stress (homocysteine, 0.6-fold; and 4-hydroxy-nonenal-glutathione, 0.4-fold) and improved mitochondrial function (1.3-fold) compared to grain-finished animals. Two potential metabolites of fluoroquinolone antibiotics, 2,8-quinolinediol and 2,8-quinolinediol sulfate, were only observed in grain-finished beef, though the source remains unknown. While pasture-finished cattle displayed improved markers of metabolic health and concentrated additional, potentially health-promoting compounds in their meat, our findings should not be interpreted as that grain-finished beef is unhealthy to consume. Randomized controlled trials in humans are required to further assess whether observed differences between pasture-finished and feedlot-finished beef have an appreciable effect on human health.

Lambda-cyhalothrin induces heart injury in chickens by regulating cytochrome P450 enzyme system and inhibiting Nrf2/HO-1 pathway

Lambda-cyhalothrin (LCT) is a common pyrethroid insecticide widely used for ectoparasite control and hygiene pest prevention in poultry and this study aimed to investigate the mechanisms of LCT-induced cardiac injury in chickens. Low, medium, and high-dose LCT exposure models in chickens were established and hematoxylin and eosin (H&E) staining, dihydroethidium (DHE) staining, TUNEL staining, immunofluorescence, biochemical analysis, and gene expression analysis were used to study the effects of LCT exposure on the chicken heart. The results showed that LCT exposure increased the serum levels of creatine kinase (CK) and lactate dehydrogenase (LDH), led to muscle fiber breakage and inflammatory cell infiltration and caused cardiac tissue damage. The DHE staining and biochemical analysis revealed that LCT exposure resulted in the excessive accumulation of ROS, decreased activities/levels of catalase (CAT), total superoxide dismutase (T-SOD), and glutathione (GSH), and increased levels of the oxidative damage marker malondialdehyde (MDA). The TUNEL staining indicated that LCT exposure increased apoptosis possibly through the elevated expression of pro-apoptotic genes in the mitochondrial pathway, the reduced expression of anti-apoptotic genes, the upregulation of pro-inflammatory factors and the downregulation of anti-inflammatory factors. Here, LCT exposure significantly inhibited the expression of genes in the Nrf2/HO-1 pathway and activated the expression of genes in the CYP450 enzyme system. Compared to the low-dose group, the high-dose LCT exposure group showed lower levels of apoptosis and inflammation, possibly related to the low oxidative stress levels mediated by the decreased expression of the CYP450 enzyme system. In conclusion, LCT exposure induces oxidative stress, apoptosis, and inflammation in chicken hearts, which may be associated with the inhibition of the Nrf2/HO-1 pathway and activation of the CYP450 enzyme system. This study provides a theoretical basis for the safer use of insecticides in poultry production.

Sexual selection may support phenotypic plasticity in male coloration of an African cichlid fish.

The expression of sexually selected traits, such as ornaments or body coloration, is often influenced by environmental conditions. While such phenotypic plasticity is often thought to precede evolutionary change, plasticity itself can also be a target of selection. However, the selective forces supporting the evolution and persistence of plasticity in sexual traits are often unclear. Using the cichlid fish Astatotilapia burtoni, we show that variation in the level of mate competition may promote plasticity in body coloration. In this species, males can change between yellow and blue colour. We found that experimentally increased competition over mating territories led to a higher proportion of males expressing the yellow phenotype. The expression of yellow coloration was found to be beneficial because yellow males won more staged dyadic contests and exhibited a lower level of oxidative stress than blue males. However, females were more likely to spawn with blue males in mate choice experiments, suggesting that expression of blue coloration is sexually more attractive. The ability to adjust colour phenotype according to the local competitive environment could therefore promote the persistence of plasticity in coloration.

Organic photovoltaic biomaterial with fullerene derivatives for near-infrared light sensing in neural cells.

Retinal degenerative diseases, which can lead to photoreceptor cell apoptosis, have now become the leading irreversible cause of blindness worldwide. In this study, we developed an organic photovoltaic biomaterial for artificial retinas, enabling neural cells to detect photoelectric stimulation. The biomaterial was prepared using a conjugated polymer donor, PCE-10, and a non-fullerene receptor, Y6, both known for their strong near-infrared light absorption capabilities. Additionally, a fullerene receptor, PC61BM, was incorporated, which possesses the ability to absorb reactive oxygen species. We conducted a comprehensive investigation into the microstructure, photovoltaic properties, and photothermal effects of this three-component photovoltaic biomaterial. Furthermore, we employed Rat adrenal pheochromocytoma cells (PC-12) as a standard neural cell model to evaluate the in vitro photoelectric stimulation effect of this photovoltaic biomaterial. The results demonstrate that the photovoltaic biomaterial, enriched with fullerene derivatives, can induce intracellular calcium influx in PC-12 cells under 630 nm (red light) and 780 nm (near-infrared) laser irradiation. Moreover, there were lower levels of oxidative stress and higher levels of mitochondrial activity compared to the non-PC61BM group. This photovoltaic biomaterial proves to be an ideal substrate for near-infrared photoelectrical stimulation of neural cells and holds promise for restoring visual function in patients with photoreceptor apoptosis.

Novel mechanistic insights into Cr(VI) and Cr(III) induced discrepancies of cellular toxicity and oxidative injury events in Eisenia fetida

Chromium (Cr) poses a high ecological risk, however the toxic mechanisms of Cr in different valence states to soil organisms at cellular and molecular levels are not exactly. In this study, the Eisenia fetida coelomocytes and Cu/Zn-superoxide dismutase (Cu/Zn-SOD) were chosen as the target subjects to investigate the effects and mechanisms of cellular toxicity induced by Cr(VI) and Cr(III). Results indicated that Cr(VI) and Cr(III) significantly reduced the coelomocytes viability. The level of reactive oxygen species (ROS) was markedly increased after Cr(VI) exposure, which finally reduced antioxidant defense abilities, and induced lipid peroxidation and cellular membrane damage in earthworm coelomocytes. However, Cr(III) induced lower levels of oxidative stress and cellular damage with respect to Cr(VI). From a molecular perspective, the binding of both Cr(VI) and Cr(III) with Cu/Zn-SOD resulted in protein backbone loosening and reduced β-Sheet content. The Cu/Zn-SOD showed fluorescence enhancement with Cr(III), whereas Cr(VI) had no obvious effect. The activity of Cu/Zn-SOD continued to decrease with the exposure of Cr. Molecular docking indicated that Cr(III) interacted more readily with the active center of Cu/Zn-SOD. Our results illustrate that oxidative stress induced by Cr(VI) and Cr(III) plays an important role in the cytotoxic differences of Eisenia fetida coelomocytes and the binding of Cr with Cu/Zn-SOD can also affect the normal structures and functions of antioxidant defense-associated protein.

The toxic effects induced by benzethonium chloride on Daphnia carinata over two generations: Resistance and higher sublethal toxicity

With the widespread utilization of the sanitizing product benzethonium chloride (BEC) throughout the coronavirus pandemic, concerns have emerged regarding its potential hazards. Nevertheless, the long-term and multigenerational toxic effects of BEC on aquatic organisms remains unexplored. This study investigates acute and chronic toxicity, oxidative stress, mitochondrial membrane potential, ATP concentrations, and gene expression using Daphnia carinata as the model organism. Meanwhile, hierarchical clustering analysis was utilized to investigate phenotypic effects among different treatment groups. The integrated biomarker response index version 2 (IBRv2) was employed to estimate the deviation in toxic effects over two generations. These results indicated that D. carinata in the second generation exhibited higher survival rate and lower levels of oxidative stress than the first generation. However, the higher sublethal effects were found in the second generation as follows, the weakened growth performance, mitochondrial membrane potential depolarization, reduced ATP concentrations, and down-regulated gene expression. The mitochondrial toxicity induced by BEC may account for the distinct toxic effects exhibited in two generations. The findings here can assist with the evaluation of potential risk for BEC on aquatic organisms, and provide new insight into the cross-generational toxicity mechanisms of pollutants in aquatic ecosystems.

NOX2 and NOX4 expression in monocytes and macrophages-extracellular vesicles in signalling and therapeutics.

Extracellular vesicles (EVs) are a type of cytoplasmic vesicles secreted by a variety of cells. EVs originating from cells have been known to participate in cell communication, antigen presentation, immune cell activation, tolerance induction, etc. These EVs can also carry the active form of Nicotinamide Adenine Dinucleotide Phosphate Oxidase Hydrogen (NADPH) oxidase, which is very essential for the production of reactive oxygen species (ROS) and that can then modulate processes such as cell regeneration. The aim of this study is to characterize the EVs isolated from U-937 and THP-1 cells, identify the NADPH oxidase (NOX) isoforms, and to determine whether EVs can modulate NOX4 and NOX2 in monocytes and macrophages. In our study, isolated EVs of U-937 were characterized using dynamic light scattering (DLS) spectroscopy and immunoblotting. The results showed that the exogenous addition of differentiation agents (either phorbol 12-myristate 13-acetate (PMA) or ascorbic acid) or the supplementation of EVs used in the study did not cause any stress leading to alterations in cell proliferation and viability. In cells co-cultured with EVs for 72h, strong suppression of NOX4 and NOX2 is evident when monocytes transform into macrophagic cells. We also observed lower levels of oxidative stress measured using immunoblotting and electron paramagnetic resonance spectroscopy under the EVs co-cultured condition, which also indicates that EVs might contribute significantly by acting as an antioxidant source, which agrees with previous studies that hypothesized the role of EVs in therapeutics. Therefore, our results provide evidence for NOX regulation by EVs in addition to its role as an antioxidant cargo.

POSSIBLE ROLES OF ANTIOXIDANTS IN ROTATOR CUFF TENDINOPATHY

The rotator cuff tendinopathy is one of the most common shoulder problems leading to full-thickness rotator cuff tendon tear and, eventually, to degenerative arthritis. Recent research on rotator cuff tendon degeneration has focused on its relationship to cell death. The types of cell death known to be associated with rotator cuff tendon degeneration are apoptosis, necrosis, and autophagic cell death. The increased incidence of cell death in degenerative tendon tissue may affect the rates of collagen synthesis and repair, possibly weakening tendon tissue and increasing the risk of tendon rupture. The biomolecular mechanisms of the degenerative changes leading to apoptotic cell death in rotator cuff tenofibroblasts have been identified as oxidative-stress-related cascade mechanisms. Furthermore, apoptosis, necrosis, and autophagic cell death are all known to be mediated by oxidative stress, a condition in which ROS (reactive oxygen species) are overproduced. Lower levels of oxidative stress trigger apoptosis; higher levels mediate necrosis. Although the signaltransduction pathway leading to autophagy has not yet been fully established, ROS are known to be essential to autophagy. A neuronal theory regarding rotator cuff degeneration has been developed from the findings that glutamate, a neural transmitter, is present in increased concentrations in tendon tissues with tendinopathy and that it induces rat supraspinatus tendon cell death. Recent studies have reported that hypoxia involved in rotator cuff tendon degeneration. Because antioxidants are known to scavenge for intracellular ROS, some studies have been conducted to determine whether antioxidants can reduce cell death in rotator cuff tendon-origin fibroblasts. The first study reported that an antioxidant has the ability to reduce apoptosis in oxidative-stressed rotator cuff tenofibroblasts. The second study reported that antioxidants have both antiapoptotic effects and antinecrotic effects on rotator cuff tendon-origin fibroblasts exposed to an oxidative stimulus. The third study reported that an antioxidant has antiautophagic-cell-death effects on rotator cuff tendon-origin fibroblasts exposed to an oxidative stimulus. The fourth study reported that glutamate markedly increases cell death in rotator cuff tendonorigin fibroblasts. The glutamate-induced cytotoxic effects were reduced by an antioxidant, demonstrating its cytoprotective effects against glutamate-induced tenofibroblast cell death. The fifth study reported that hypoxia significantly increases intracellular ROS and apoptosis. The hypoxia-induced cytotoxic effects were markedly attenuated by antioxidants, demonstrating their cytoprotective effects against hypoxia-induced tenofibroblast cell death. In conclusion, antioxidants have cytoprotective effects on tenofibroblasts exposed in vitro to an oxidative stressor, a neurotransmitter, or hypoxia. These cytoprotective effects result from antiapoptotic, antinecrotic, and antiautophagic actions involving the inhibition of ROS formation. These findings suggest that antioxidants may have therapeutic potential for rotator cuff tendinopathy. Further studies must be conducted in order to apply these in vitro findings to clinical situations.

Does dietary total antioxidant capacity relate to oxidative stress levels in water immersion during labor? A case-control study.

The aim of this study was to investigate the effect of water immersion during the first stage of labor on maternal and neonatal oxidative stress and the association between serum and dietary total antioxidant capacity. Women were divided into two groups: those immersed in water during the first stage of labor (n=30) and those who had conventional birth (n=33). Total oxidative stress and total antioxidant status levels were examined in antepartum and postpartum maternal serum and neonatal cord blood samples. Dietary total antioxidant capacity was determined by the food frequency questionnaire. Vitamin C and dietary total antioxidant capacity consumption were found to be higher in the water immersion group (106.92 mg/day and 18.94 mmol/gün, respectively) than the conventional birth group (92.69 mg/day and 15.99 mmol/gün, respectively) (p<0.05). Women immersed in water during the first stage of labor had lower total oxidative stress levels in antepartum and postpartum maternal serum and neonatal cord blood samples than those who had conventional birth (5.43±2.42 mmol/L and 5.59±3.35 mmol/L vs. 8.58±5.53 mmol/L and 12.68±16.58 mmol/L; p<0.05). Dietary total antioxidant capacity was found to be negatively correlated with total oxidative stress levels in antepartum and postpartum maternal serum and neonatal cord blood samples (p=0.012, p=0.047, p=0.035, and p<0.05). Women immersed in water during the first stage of labor had lower total oxidative stress levels in their postnatal maternal serum and neonatal cord blood samples and dietary total antioxidant capacity was also a factor associated with low total oxidative stress levels.

Empagliflozin alone and in combination with metformin ameliorate diabetes type 2-oxidative stress

Currently, one of the major public health concerns is diabetes mellitus, which is known as a silent killer due to the failure to diagnose it at an early stage. A growing body of research indicates that metformin and empagliflozin have antioxidant properties in addition to their hypoglycemic properties. Our research looked into the potential antioxidant effects of metformin and empagliflozin on diabetic rats by decreasing oxidative stress. For eight weeks, 42 adult male Sprague Dawley rats were divided into six groups: normal control, diabetic control group, diabetic group received dimethyl sulfoxide as a vehicle(solvent) of the empagliflozin, 250 mg/kg metformin only, 10 mg/kg empagliflozin only and a combination of both. A single injection of 40 mg/kg streptozocin administered intraperitoneally was after administering 10% fructose in drinking water for two weeks to cause type 2 diabetes in rats. The evaluation of oxidative stress involved the quantification of serum malondialdehyde (MDA) and superoxide dismutase (SOD) levels upon completion of the experimental period. Additionally, blood glucose levels were determined using blood samples from the tail, and body weight was monitored on a weekly basis. Our findings showed that compared to the diabetic group, the therapy groups had considerably lower blood glucose, and serum MDA levels, while higher levels of SOD, and less decrease in body weight. Furthermore, even better results were obtained when empagliflozin and metformin were administered together. As a result of our findings, diabetic rats treated with empagliflozin and metformin had lower levels of oxidative stress.

Satellite III (1q12) Copy Number Variation in Cultured Human Skin Fibroblasts from Schizophrenic Patients and Healthy Controls.

The chromosome 1q12 region harbors the genome's largest pericentromeric heterochromatin domain that includes tandemly repeated satellite III DNA [SatIII (1)]. Increased SatIII (1) copy numbers have been found in cultured human skin fibroblasts (HSFs) during replicative senescence. The aim of this study was to analyze the variation in SatIII (1) abundance in cultured HSFs at early passages depending on the levels of endogenous and exogenous stress. We studied 10 HSF cell lines with either high (HSFs from schizophrenic cases, n = 5) or low (HSFs from healthy controls, n = 5) levels of oxidative stress. The levels of endogenous stress were estimated by the amounts of reactive oxygen species, DNA damage markers (8-hydroxy-2'-deoxyguanosine, gamma-H2A histone family member X), pro- and antioxidant proteins (NADPH oxidase 4, superoxide dismutase 1, nuclear factor erythroid 2-related factor 2), and proteins that regulate apoptosis and autophagy (B-cell lymphoma 2 [Bcl-2], Bcl-2-associated X protein, light chain 3). SatIII (1) copy numbers were measured using the nonradioactive quantitative hybridization technique. For comparison, the contents of telomeric and ribosomal RNA gene repeats were determined. RNASATIII (1 and 9) were quantified using quantitative Polymerase Chain Reaction (PCR). Increased SatIII (1) contents in DNA from confluent HSFs were positively correlated with increased oxidative stress. Confluent cell cultivation without medium replacement and heat shock induced a decrease of SatIII (1) in DNA in parallel with a decrease in RNASATIII (1) and an increase in RNASATIII (9). During HSF cultivation, cells with increased SatIII (1) content accumulated in the cell pool under conditions of exaggerated oxidative stress. This fraction of cells decreased after the additional impact of exogenous stress. The process seems to be oscillatory.

Identification of Compounds Protecting Pancreatic Islets against Oxidative Stress using a 3D Pseudoislet Screening Platform.

Oxidative stress leads to a lower success rate of clinical islet transplantation. Here, FDA-approved compounds are screened for their potential to decrease oxidative stress and to protect or enhance pancreatic islet viability and function. Studies are performed on in vitro "pseudoislet" spheroids, which are pre-incubated with 1280 different compounds and subjected to oxidative stress. Cell viability and oxidative stress levels are determined using a high-throughput fluorescence microscopy pipeline. Initial screening on cell viability results in 59 candidates. The top ten candidates are subsequently screened for their potential to decrease induced oxidative stress, and eight compounds efficient reduction of induced oxidative stress in both alpha and beta cells by 25-50%. After further characterization, the compound sulfisoxazole is found to be the most capable of reducing oxidative stress, also at short pre-incubation times, which is validated in primary human islets, where low oxidative stress levels and islet function are maintained. This study shows an effective screening strategy with 3D cell aggregates based on cell viability and oxidative stress, which leads to the discovery of several compounds with antioxidant capacity. The top candidate, sulfisoxazole is effective after a 30 min pre-incubation, maintains baseline islet function, and may help alleviate oxidative stress in pancreatic islets.

Identifying oxidative stress-related biomarkers in idiopathic pulmonary fibrosis in the context of predictive, preventive, and personalized medicine using integrative omics approaches and machine-learning strategies.

Idiopathic pulmonary fibrosis (IPF) is a rare interstitial lung disease with a poor prognosis that currently lacks effective treatment methods. Preventing the acute exacerbation of IPF, identifying the molecular subtypes of patients, providing personalized treatment, and developing individualized drugs are guidelines for predictive, preventive, and personalized medicine (PPPM/3PM) to promote the development of IPF. Oxidative stress (OS) is an important pathological process of IPF. However, the relationship between the expression levels of oxidative stress-related genes (OSRGs) and clinical indices in patients with IPF is unclear; therefore, it is still a challenge to identify potential beneficiaries of antioxidant therapy. Because PPPM aims to recognize and manage diseases by integrating multiple methods, patient stratification and analysis based on OSRGs and identifying biomarkers can help achieve the above goals. Transcriptome data from 250 IPF patients were divided into training and validation sets. Core OSRGs were identified in the training set and subsequently clustered to identify oxidative stress-related subtypes. The oxidative stress scores, clinical characteristics, and expression levels of senescence-associated secretory phenotypes (SASPs) of different subtypes were compared to identify patients who were sensitive to antioxidant therapy to conduct differential gene functional enrichment analysis and predict potential therapeutic drugs. Diagnostic markers between subtypes were obtained by integrating multiple machine learning methods, their expression levels were tested in rat models with different degrees of pulmonary fibrosis and validation sets, and nomogram models were constructed. CIBERSORT, single-cell RNA sequencing, and immunofluorescence staining were used to explore the effects of OSRGs on the immune microenvironment. Core OSRGs classified IPF into two subtypes. Patients classified into subtypes with low oxidative stress levels had better clinical scores, less severe fibrosis, and lower expression of SASP-related molecules. A reliable nomogram model based on five diagnostic markers was constructed, and these markers' expression stability was verified in animal experiments. The number of neutrophils in the immune microenvironment was significantly different between the two subtypes and was closely related to the degree of fibrosis. Within the framework of PPPM, this work comprehensively explored the role of OSRGs and their mediated cellular senescence and immune processes in the progress of IPF and assessed their capabilities aspredictors of high oxidative stress and disease progression,targets of the vicious loop between regulated pulmonary fibrosis and OS for targeted secondary and tertiary prevention, andreferences for personalized antioxidant and antifibrotic therapies. The online version contains supplementary material available at 10.1007/s13167-023-00334-4.

Oxidative Stress and Performance after Training in Professional Soccer (European Football) Players.

Vitamins, hormones, free radicals, and antioxidant substances significantly influence athletic performance. The aim of this study was to evaluate whether these biological mediators changed during the season and if this was associated with the rate of improvement in performance after training, assessed by means of a standardized test. Professional male soccer players took part in the study. Two evaluations were performed: the first in the pre-season period and the second at the mid-point of the official season, after about 6 months of intensive training and weekly matches. Blood levels of vitamins D, B12, and folic acid, testosterone and cortisol, free radicals, and antioxidant substances were measured. Two hours after breakfast, a Yo-Yo test was performed. The relationships between the biological mediators and the rate of improvement after training (i.e., the increase in meters run in the Yo-Yo test between the pre-season and mid-season periods) were evaluated by means of a linear mixed models analysis. Results: Eighty-two paired tests were performed. The athletes showed better performance after training, with an increase in the meters run of about 20%. No significant relationships between the vitamin and hormone values and the gain in the performance test were observed. Plasmatic levels of free radicals increased significantly, as did the blood antioxidant potential. An indirect relationship between oxidative stress and the improvement in performance was observed (free radicals β ± SE: = -0.33 ± 0.10; p-value = 0.001), with lower levels of oxidative stress being associated with higher levels of performance in the Yo-Yo test. Monitoring the measures of oxidative stress could be a useful additional tool for coaches in training and/or recovery programs tailored to each player.

The Interplay of Exogenous and Endogenous Hydrogen Sulfide (H2S) in Maintaining Redox Homeostasis in Individuals with Low Ferritin Levels

The primary objective of this study was to investigate the influence of living near a thermal spring and being exposed to hydrogen sulfide (H2S) gas, which lingers in the surrounding atmosphere, on the redox and lipid peroxidation status of individuals with low ferritin levels. Participants in the study were divided into two groups based on their H2S exposure frequency and ferritin levels. Within Group A, individuals who did not experience occasional H2S exposure (2–3 h, 2–3 times per year) and had an average of normal ferritin levels of 87.5 ng/mL exhibited lower levels of oxidative stress and lipid peroxidation compared to those with low ferritin levels (average of 6.57 ng/mL) in the same group. Additionally, individuals with normal ferritin levels showed higher levels of thiol, H2S, and antioxidant capacity. However, it was observed that individuals with low ferritin levels had significantly lower levels of endogenous H2S and thiol and higher levels of oxidative stress and lipid peroxidation. In Group B, individuals who experienced occasional H2S exposure (2–3 h, 10–12 times per year) and had an average of normal ferritin levels of 91.65 ng/mL showed lower oxidative stress and lipid peroxidation, as well as higher thiol, H2S, and antioxidant capacity. Surprisingly, individuals in Group B with low ferritin levels (average of 6.18 ng/mL) showed increased endogenous levels of H2S, which resulted in lower oxidative stress, and lipid peroxidation. These findings suggest that inhaling environmental H2S emitted from thermal springs may serve as an adaptive and protective mechanism for individuals with low ferritin levels by enhancing antioxidant capacity and reducing oxidative stress and lipid peroxidation modification, thus mitigating the harmful effects of reactive oxygen species.