Arsenic exposure and oxidative damage to lipid, DNA, and protein among general Chinese adults: A repeated-measures cross-sectional and longitudinal study.

Arsenic-related oxidative stress and resultant diseases have attracted global concern, while longitudinal studies are scarce. To assess the relationship between arsenic exposure and systemic oxidative damage, we performed two repeated measures among 5236 observations (4067 participants) in the Wuhan-Zhuhai cohort at the baseline and follow-up after 3 years. Urinary total arsenic, biomarkers of DNA oxidative damage (8-hydroxy-2'-deoxyguanosine (8-OHdG)), lipid peroxidation (8-isoprostaglandin F2alpha (8-isoPGF2α)), and protein oxidative damage (protein carbonyls (PCO)) were detected for all observations. Here we used linear mixed models to estimate the cross-sectional and longitudinal associations between arsenic exposure and oxidative damage. Exposure-response curves were constructed by utilizing the generalized additive mixed models with thin plate regressions. After adjusting for potential confounders, arsenic level was significantly and positively related to the levels of global oxidative damage and their annual increased rates in dose-response manners. In cross-sectional analyses, each 1% increase in arsenic level was associated with a 0.406% (95% confidence interval (CI): 0.379% to 0.433%), 0.360% (0.301% to 0.420%), and 0.079% (0.055% to 0.103%) increase in 8-isoPGF2α, 8-OHdG, and PCO, respectively. More importantly, arsenic was further found to be associated with increased annual change rates of 8-isoPGF2α (ß: 0.147; 95% CI: 0.130 to 0.164), 8-OHdG (0.155; 0.118 to 0.192), and PCO (0.050; 0.035 to 0.064) in the longitudinal analyses. Our study suggested that arsenic exposure was not only positively related with global oxidative damage to lipid, DNA, and protein in cross-sectional analyses, but also associated with annual increased rates of these biomarkers in dose-dependent manners.

Cognitive Benefits of Folic Acid, Docosahexaenoic Acid, and a Combination of Both Nutrients in Mild Cognitive Impairment: Possible Alterations through Mitochondrial Function and DNA Damage.

INTRODUCTION: It is uncertain whether folic acid (FA) combined with docosahexaenoic acid (DHA) could improve cognitive performance. This study evaluated the effects of a 12-month FA and DHA supplementation, in combination or alone, on cognitive function, DNA oxidative damage, and mitochondrial function in participants with mild cognitive impairment (MCI). METHODS: This randomized, double-blind, placebo-controlled trial recruited MCI participants aged 60 years and older. Two hundred and eighty participants were randomly divided in equal proportion into four groups: FA + DHA (FA 800 µg/d + DHA 800 mg/d), FA (800 µg/d), DHA (800 mg/d), and placebo groups daily orally for 12 months. The primary outcome was cognitive function evaluated by the Wechsler Adult Intelligence Scale-Revised (WAIS-RC). Cognitive tests and blood mechanism-related biomarkers were determined at baseline and 12 months. RESULTS: During the 12-month follow-up, scores of full intelligence quotient (ßDHA: 1.302, 95% CI: 0.615, 1.990, p < 0.001; ßFA: 1.992, 95% CI: 1.304, 2.679, p < 0.001; ßFA+DHA: 2.777, 95% CI: 2.090, 3.465, p < 0.001), verbal intelligence quotient, and some subtests of the WAIS-RC were significantly improved in FA + DHA and single intervention groups compared to the placebo group. Moreover, the FA and DHA intervention combination was superior to either intervention alone (p < 0.001). Meanwhile, FA, DHA, and their combined use significantly decreased 8-OHdG level and increased mitochondrial DNA copy number compared to the placebo (p < 0.05). CONCLUSIONS: Supplementation of FA and DHA, alone or combined, for 12 months can improve cognitive function in MCI participants, possibly through mitigating DNA oxidative damage and enhancing mitochondrial function. Combined supplementation may provide more cognitive benefit than supplementation alone.

Cardiomyocyte-specific overexpression of FPN1 diminishes cardiac hypertrophy induced by chronic intermittent hypoxia.

The significance of iron in myocardial mitochondria function cannot be underestimated, because deviations in iron levels within cardiomyocytes may have profound detrimental effects on cardiac function. In this study, we investigated the effects of ferroportin 1 (FPN1) on cardiac iron levels and pathological alterations in mice subjected to chronic intermittent hypoxia (CIH). The cTNT-FPN1 plasmid was administered via tail vein injection to induce the mouse with FPN1 overexpression in the cardiomyocytes. CIH was established by exposing the mice to cycles of 21%-5% FiO2 for 3 min, 8 h per day. Subsequently, the introduction of hepcidin resulted in a reduction in FPN1 expression, and H9C2 cells were used to establish an IH model to further elucidate the role of FPN1. First, FPN1 overexpression ameliorated CIH-induced cardiac dysfunction, myocardial hypertrophy, mitochondrial damage and apoptosis. Second, FPN1 overexpression attenuated ROS levels during CIH. In addition, FPN1 overexpression mitigated CIH-induced cardiac iron accumulation. Moreover, the administration of hepcidin resulted in a reduction in FPN1 levels, further accelerating the CIH-induced levels of ROS, LIP and apoptosis in H9C2 cells. These findings indicate that the overexpression of FPN1 in cardiomyocytes inhibits CIH-induced cardiac iron accumulation, subsequently reducing ROS levels and mitigating mitochondrial damage. Conversely, the administration of hepcidin suppressed FPN1 expression and worsened cardiomyocyte iron toxicity injury.

Deciphering the alleviation potential of nitric oxide, for low temperature and chromium stress via maintaining photosynthetic capacity, antioxidant defence, and redox homeostasis in rice (Oryza sativa).

Sodium nitroprusside (SNP) is a potent nitric oxide (NO) donor that enhances plant tolerance to various abiotic stresses. This research aims to assess the effect of SNP application on rice seedlings subjected to individual and combined exposure to two abiotic stresses viz., low-temperature (LT) and chromium (Cr). Exposure to LT, Cr, and LT+Cr caused severe oxidative damage by stimulating greater production and accumulation of reactive oxygen species (ROS) leading to lipid peroxidation and cell membrane instability. The combined LT+CR stress more intensly increased the cellular oxidative stress and excessive Cr uptake that in turn deteriorated the chlorophyll pigments and photosynthesis, as well as effected the level of tetrapyrrole biosynthesis in rice plants. The reduction in rice seedling growth was more obvious under LT+Cr treatment than their individual effects. The exogenous application of SNP diminished the toxic impact of LT and Cr stress. This was attributed to the positive role of SNP in regulating the endogenous NO levels, free amino acids (FAAs) contents, tetrapyrrole biosynthesis and antioxidants. Consequently, SNP-induced NO decreased photorespiration, ROS generation, lipid peroxidation, and electrolyte leakage. Moreover, exogenous SNP diminished the Cr uptake and accumulation by modulating the ionic homeostasis and strengthening the heavy metals detoxification mechanism, thus improving plant height, biomass and photosynthetic indexes. Essentially, SNP boosts plant tolerance to LT and Cr stress by regulating antioxidants, detoxification mechanism, and the plant's physio-biochemical. Hence, applying SNP is an effective method for boosting rice plant resilience and productivity in the face of escalating environmental stresses and pollutants.

Isolation, Characterization, and Functional Properties of Antioxidant Peptides from Mulberry Leaf Enzymatic Hydrolysates.

Recent evidence suggests that mulberry leaves have good antioxidant activity. However, what the antioxidant ingredient is and how the ingredient works are still not well understood. In this study, we enzymatically hydrolyze mulberry leaf proteins (MLPs) using neutral protease and find that the mulberry leaf protein hydrolysates (MLPHs) have stronger antioxidant activity compared to MLPs. We separate the core antioxidant components in MLPHs by ion-exchange columns and molecular sieves and identify 798 antioxidant peptides by LC-MS/MS. Through bioinformatics analysis and biochemical assays, we screen two previously unreported peptides, P6 and P7, with excellent antioxidant activities. P6 and P7 not only significantly reduce ROS in cells but also improve the activities of the antioxidant enzymes SOD and CAT. In addition, both peptides are found to exert protective effects against H2O2-induced chromatin damage and cell apoptosis. Collectively, these results provide support for the application of mulberry leaf peptides as antioxidants in the medical, food and livestock industries.

Ten "Cheat Codes" for Measuring Oxidative Stress in Humans.

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

Nicotinamide riboside alleviates ionizing radiation-induced intestinal senescence by alleviating oxidative damage and regulating intestinal metabolism.

INTRODUCTION: The intestine, frequently subjected to pelvic or abdominal radiotherapy, is particularly vulnerable to delayed effects of acute radiation exposure (DEARE) owing to its high radiation sensitivity. Radiation-induced intestinal senescence, a result of DEARE, profoundly affects the well-being and quality of life of radiotherapy patients. However, targeted pharmaceutical interventions for radiation-induced senescence are currently scarce. Our findings showcase that nicotinamide riboside(NR) effectively alleviates radiation-induced intestinal senescence, offering crucial implications for utilizing NR as a pharmacological agent to combat intestinal DEARE. OBJECTIVES: The aim of this study was to investigate the ability of NR to reduce radiation induced intestinal senescence and explore its related mechanisms. METHODS: Male C57BL/6J mice were randomly divided into CON, IR, and IR + NR groups. The mice in the IR and IR + NR groups were subjected to a 6.0 Gy γ-ray total body exposure. After 8 weeks, the mice in the IR + NR group received NR via gavage at a dose of 400 mg/kg/d for 21 days. Then the mice were used for sample collection. RESULTS: Our results demonstrate that NR can significantly mitigate radiation-induced intestinal senescence. Furthermore, our findings indicate that NR can mitigate oxidative damage, restore the normal function of intestinal stem cells, regulate the disruption of the intestinal symbiotic ecosystem and address metabolic abnormalities. In addition, the underlying mechanisms involve the activation of SIRT6, SIRT7 and the inhibition of the mTORC1 pathway by NR. CONCLUSION: In conclusion, our results reveal the substantial inhibitory effects of NR on radiation-induced intestinal senescence. These findings offer valuable insights into the potential therapeutic use of NR as a pharmacological agent for alleviating intestinal DEARE.

Activation of the Neuronal Cell Cycle in Brains in Amnestic Mild Cognitive Impairment: Early Involvement in the Progression of Alzheimer's Disease.

Activation of cell-cycle machinery in Alzheimer's disease (AD) brain was reported by Mark Smith and colleagues and by other researchers. Among other biochemical processes underlying this activation, the notion that AD brain, under the onslaught of oxidative and nitrosative damage leading to neuronal loss, neurons would attempt to replenish their numbers by entering the cell cycle. However, being post-mitotic, neurons entering the cell cycle would become trapped therein, ultimately leading to death of these neurons. Yang and co-workers and the Butterfield laboratory first reported that similar activation of the cell cycle was present in the brains of individuals with amnestic mild cognitive impairment (MCI), arguably the earliest clinical stage of AD, but who demonstrate normal activities of daily living and no dementia. Activation of the cell cycle in MCI brain is consonant with the concept that this process is an early aspect in the progression of AD. This brief review article discusses these findings and recognizes the contribution of Dr. Mark Smith to the investigation of cell-cycle activation in AD brain and other aspects of AD neuropathology.

Consilience and unity in ocular anterior segment research.

In his beautiful book, Consilience: The Unity of Knowledge, the eminent biologist Edward O Wilson, advocates the need for integration and reconciliation across the sciences. He defines consilience as "literally a 'jumping together' of knowledge with a linking of facts ... to create a common groundwork of explanation". It is the premise of this paper that as much as basic biomedical research is in need of data generation using the latest available techniques- unifying available knowledge is just as critical. This involves the necessity to resolve contradictory findings, reduce silos, and acknowledge complexity. We take the cornea and the lens as case studies of our premise. Specifically, in this perspective, we discuss the conflicting and fragmented information on protein aggregation, oxidative damage, and fibrosis. These are fields of study that are integrally tied to anterior segment research. Our goal is to highlight the vital need for Wilson's consilience and unity of knowledge which in turn should lead to enhanced rigor and reproducibility, and most importantly, to greater understanding and not simply knowing.

Early life thermal conditioning alters heat-shock protein expression in response to an adult thermal stressor.

Developmental environmental stressors can have instructive effects on an organism's phenotype. This developmental plasticity can prepare organisms for potentially stressful future environments, circumventing detrimental effects on fitness. However, the physiological mechanisms underlying such adaptive plasticity are understudied, especially in vertebrates. We hypothesized that captive male zebra finches (Taeniopygia castanotis) exposed to a mild heat conditioning during development would acquire a persisting thermotolerance, and exhibit increased heat-shock protein (HSP) levels associated with a decrease in oxidative damage when exposed to a high-intensity stressor in adulthood. To test this, we exposed male finches to a prolonged mild heat conditioning (38°C) or control (22°C) treatment as juveniles. Then in a 2 × 2 factorial manner, these finches were exposed to a high heat stressor (42°C) or control (22°C) treatment as adults. Following the adult treatment, we collected testes and liver tissue and measured HSP70, HSP90, and HSP60 protein levels. In the testes, finches exhibited lower levels of HSP90 and HSP60 when exposed to the high heat stressor in adulthood if they were exposed to the mild heat conditioning as juveniles. In the liver, finches exposed to the high heat stressor in adulthood had reduced HSP90 and HSP60 levels, regardless of whether they were conditioned as juveniles. In some cases, elevated testes HSP60 levels were associated with increased liver oxidative damage and diminishment of a condition-dependent trait, indicating potential stress-induced tradeoffs. Our results indicate that a mild conditioning during development can have persisting effects on HSP expression and acquired thermotolerance.

Foliar Application of Chitosan (CTS), γ-Aminobutyric Acid (GABA), or Sodium Chloride (NaCl) Mitigates Summer Bentgrass Decline in the Subtropical Zone.

Creeping bentgrass (Agrostis stolonifera) is an excellent cool-season turfgrass that is widely used in urban gardening, landscaping, and golf turf. Triennial field experiments from 2017 to 2019 were conducted to investigate effects of the foliar application of chitosan (CTS), γ-aminobutyric acid (GABA), or sodium chloride (NaCl) on mitigating summer bentgrass decline (SBD) and exploring the CTS, GABA, or NaCl regulatory mechanism of tolerance to summer heat stress associated with changes in chlorophyll (Chl) loss and photosynthetic capacity, osmotic adjustment (OA), oxidative damage, and cell membrane stability. The findings demonstrated that persistent ambient high temperatures above 30 °C during the summer months of 2017, 2018, and 2019 significantly reduced the turf quality (TQ), Chl content, photochemical efficiency of PSII (Fv/Fm and PIABS), leaf relative water content, and osmotic potential (OP) but significantly increased electrolyte leakage (EL) and the accumulations of free proline, water-soluble carbohydrate (WSC), hydrogen peroxide (H2O2), and malondialdehyde (MDA). The foliar application of CTS, GABA, or NaCl could significantly alleviate SBD, as reflected by improved TQ and delayed Chl loss during hot summer months. Heat-induced declines in Fv/Fm, PIABS, the net photosynthetic rate (Pn), the transpiration rate (Tr), and water use efficiency (WUE) could be significantly mitigated by the exogenous application of CTS, GABA, or NaCl. In addition, the foliar application of CTS, GABA, or NaCl also significantly improved the accumulations of free proline and WSC but reduced the EL, OP, and H2O2 content and the MDA content in leaves of creeping bentgrass in favor of water and redox homeostasis in summer. Based on the comprehensive evaluation of the subordinate function value analysis (SFVA), the CTS had the best effect on the mitigation of SBD, followed by GABA and NaCl in 2017, 2018, and 2019. The current study indicates that the foliar application of an appropriate dose of GABA, CTS, or NaCl provides a cost-effective strategy for mitigating SBD.

Temporary alleviation of MAPK by arbutin alleviates oxidative damage in the retina and ARPE-19 cells.

Dry age-related macular degeneration (AMD) is one of the main diseases that causes blindness in humans, and the number of cases is increasing yearly. However, effective treatments are unavailable, and arbutin (ARB) has been reported to have antioxidant, anti-inflammatory, and anti-aging effects in other age-related diseases. However, whether ARB can be used to treat dry AMD remains unknown. To explore the therapeutic potential and molecular mechanism of arbutin in the treatment of dry AMD. MTT assays, reactive oxygen species (ROS) production assays, flow cytometry assays, qPCR and western blotting were used to assess the impact of ARB on human RPECs induced by H2O2. A transcriptome sequencing assay was used to further explore how ARB acts on human RPECs treated with H2O2. Hematoxylin and eosin (H&E) staining and total antioxidant capacity (T-AOC) assays were used to observe the impact of ARB on mouse retina induced by sodium iodate. ARB counteracted the H2O2-induced reduction in human RPECs viability, ARB reversed H2O2-induced cellular ROS production by increasing the expression of antioxidant-related genes and proteins, ARB also reversed H2O2-induced cell apoptosis by altering the expression of apoptosis-related genes and proteins. Transcriptome sequencing and western blotting showed that ARB reduced ERK1/2 and P-38 phosphorylation to prevent H2O2-induced oxidation damage. The in vivo experiments demonstrated that ARB protected against retinal morphology injury in mice, increased serum T-AOC levels and increased antioxidant oxidase gene expression levels in the mouse retina induced by sodium iodate. We concluded that ARB reversed the H2O2-induced decrease in human RPECs viability through the inhibition of ROS production and apoptosis. The ERK1/2 and P38 MAPK signaling pathways may mediate this process. ARB maintained retinal morphology, increased serum T-AOC level and improved the expression of antioxidant oxidase genes in mice.

Identification of spontaneous age-related cataract in Microtus fortis. / ä¸œæ–¹ç”°é¼ è‡ªå‘æ€§å¹´é¾„ç›¸å ³æ€§ç™½å† éšœçš„é‰´å®š.

OBJECTIVES: Age-related cataract is the most common type of adult cataract and a leading cause of blindness. Currently, there are few reports on the establishment of animal models for age-related cataract. During the experimental breeding of Microtus fortis (M. fortis), we first observed that M. fortis aged 12 to 15 months could naturally develop cataracts. This study aims to explore the possibility of developing them as an animal model for age-related cataract via identifing and analyzing spontaneous cataract in M. fortis. METHODS: The 12-month-old healthy M. fortis were served as a control group and 12-month-old cataractous M. fortis were served as an experimental group. The lens transparency was observed using the slit-lamp biomicroscope. Hematoxylin and eosin staining was used to detect pathological changes in the lens. Biochemical detection methods were applied to detect blood routine, blood glucose levels, the serum activities of superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) in both groups. Finally, real-time RT-PCR was used to detect the transcription levels of cataract-related genes in the lens of 2 groups. RESULTS: Compared with the control group, the lens of cataract M. fortis showed severely visible opacity, the structure of lens was destroyed seriously, and some pathological damage, such as swelling, degeneration/necrosis, calcification, hyperplasia, and fiber liquefaction were found in lens epithelial cells (LECs). The fibrous structure was disorganized and irregularly distributed with morgagnian globules (MGs) aggregated in the degenerated lens fibers. There was no statistically significant difference in blood glucose levels between the experimental and control groups (P>0.05). However, white blood cell (WBC) count (P<0.05), lymphocyte count (P<0.01), and lymphocyte ratio (P<0.05) were significantly decreased, while neutrophil percentage (P<0.05) and monocyte ratio (P<0.01) were significantly increased. The serum activities of SOD and GSH-Px (both P<0.05) were both reduced. The mRNAs of cataract-related genes, including CRYAA, CRYBA1, CRYBB3, Bsfp1, GJA3, CRYBA2, MIP, HspB1, DNase2B, and GJA8, were significantly downregultaed in the lenses of the experimental group (all P<0.05). CONCLUSIONS: There are significant differences in lens pathological changes, peroxidase levels, and cataract-related gene expression between cataract and healthy M. fortis. The developed cataract spontaneously in M. fortis is closely related to age, the cataract M. fortis might be an ideal animal model for the research of age-related cataract.

Combined effects of heatwaves and atmospheric CO2 levels on Brassica juncea phytoremediation.

Heatwaves, expected to become more frequent, pose a significant threat to plant biomass production. This experiment was designed to estimate heatwave influence on Brassica juncea phytoremediation when superimposed on different CO2 levels. A 7-day heatwave was generated during the species flowering stage. Heatwaves decreased all B. juncea dry weights. The lowest species dry weight was recorded when the heatwave was accompanied by 250 ppm CO2, in which the biomass significantly decreased by 40.0% relative to that of no heatwave under the same atmospheric CO2 conditions. Heatwave superposition with 250 ppm CO2 reduced the Cd content in B. juncea aerial parts by 28.1% relative to that of identical environmental conditions without heatwave, whereas the opposite result was observed under 550 ppm CO2 conditions. The heatwave caused oxidative damage to B. juncea under all CO2 conditions, as manifested by increased malondialdehyde levels in the plant shoots. With heatwave superposition, antioxidant enzyme activity was enhanced by exposure to 400 and 550 ppm CO2. Considering biomass yield generation and Cd uptake capacity, heatwave superposition decreased the B. juncea phytoremediation effects, and high atmospheric CO2 conditions could alleviate detrimental effects to a certain extent. This study uniquely examines the combined effects of heatwaves and varying CO2 levels on phytoremediation, providing microscopic insights into oxidative damage and enzyme activity, highlighting the potential for CO2 enrichment to mitigate heatwave impacts, and offering comprehensive analysis for future agricultural practices and environmental management.

Study on the metabolic effects of hexavalent chromium [Cr (VI)] on rat astrocytes using un-targeted metabolomics.

Introduction: Hexavalent chromium [Cr (VI)] has been identified as a human carcinogen and environmental pollutant capable of affecting multiple systems in the human body. However, the specific mechanisms by which Cr (VI) affects the human nervous system remain unclear. Objective: Following confirmation of Cr (VI)'s toxic effects on rat astrocytes, this study explores the metabolites and associated metabolic pathways of rat astrocytes under different doses of Cr (VI) exposure. Methods: Cell viability was assessed using CCK8 assays, intracellular reactive oxygen species (ROS) levels were measured using DCFH-DA fluorescent probes, intracellular 8-hydroxydeoxyguanosine (8-OHdG) content was determined by Elisa, mitochondrial membrane potential was observed using JC-1 probes, and key metabolites were identified through untargeted metabolomics analysis. Results: With increasing Cr (VI) doses, significant decreases in cell viability were observed in the 4, 8, and 16 mg/L dose groups (p < 0.05). Elevated levels of ROS and 8-OHdG, increased caspase-3 activity, and significant reductions in mitochondrial membrane potential were observed in the 2 and 4 mg/L dose groups (p < 0.05). Untargeted metabolomics analysis revealed Cr (VI)'s impact on key metabolites such as sphingosine and methionine. Enrichment analysis of KEGG pathways highlighted the critical roles of sphingolipid metabolism and the methionine-cysteine cycle in the effects of Cr (VI) on rat astrocytes. Conclusion: Our study underscores the potential neuro-health risks associated with environmental and occupational exposure to Cr (VI) and provides new perspectives and directions for investigating neurotoxic mechanisms.

Effects of Multivitamin-Mineral Supplementation on Chronic Stress-Induced Oxidative Damage in Swiss Albino Mice.

OBJECTIVE: Stress is a hazardous occurrence that causes a variety of physiological and behavioral responses in a person. It increases energy metabolism and enhances oxidative stress, both of which are implicated in the pathophysiology of several diseases. Numerous vitamins and minerals have the ability to modulate oxidative stress. The present investigation aimed to evaluate the effectiveness of a multivitamin-mineral (MM) supplement in addressing oxidative imbalances caused by chronic stress in the plasma, hepatic, and renal tissues of Swiss albino mice. METHODS: Thirty healthy male Swiss albino mice were randomly assigned to one of the three groups, with 10 animals each: control, unpredictable chronic stress (UCS), and MM + UCS. The experiment lasted for four weeks, after which all the animals underwent cervical decapitation, and samples of their blood, liver, and kidney were taken for biochemical studies. DNA damage analysis was performed on lymphocytes. RESULTS: Exposure to UCS negatively affected all biochemical markers, as indicated by reduced levels of antioxidants (superoxide dismutase, catalase, glutathione S-transferase, glutathione reductase, and reduced glutathione) in the plasma, liver, and kidney tissues, along with enhanced levels of lipid peroxidation and marker enzymes. MM supplementation normalized the deranged biochemical markers in stress-exposed mice. The results of DNA damage supported the biochemical findings mentioned above. CONCLUSION: The findings suggest that MM supplementation could help reduce oxidative disturbances caused by stress in both healthy and diseased conditions.

Prodromic Inflammatory-Oxidative Stress in Peritoneal Leukocytes of Triple-Transgenic Mice for Alzheimer's Disease.

Inflammatory-oxidative stress is known to be pivotal in the pathobiology of Alzheimer's disease (AD), but the involvement of this stress at the peripheral level in the disease's onset has been scarcely studied. This study investigated the pro-inflammatory profile and oxidative stress parameters in peritoneal leukocytes from female triple-transgenic mice for AD (3xTgAD) and non-transgenic mice (NTg). Peritoneal leukocytes were obtained at 2, 4, 6, 12, and 15 months of age. The concentrations of TNFα, INFγ, IL-1ß, IL-2, IL-6, IL-17, and IL-10 released in cultures without stimuli and mitogen concanavalin A and lipopolysaccharide presence were measured. The concentrations of reduced glutathione (GSH), oxidized glutathione (GSSG), lipid peroxidation, and Hsp70 were also analyzed in the peritoneal cells. Our results showed that although there was a lower release of pro-inflammatory cytokines by 3xTgAD mice, this response was uncontrolled and overstimulated, especially at a prodromal stage at 2 months of age. In addition, there were lower concentrations of GSH in leukocytes from 3xTgAD and higher amounts of lipid peroxides at 2 and 4 months, as well as, at 6 months, a lower concentration of Hsp70. In conclusion, 3xTgAD mice show a worse pro-inflammatory response and higher oxidative stress than NTg mice during the prodromal stages, potentially supporting the idea that Alzheimer's disease could be a consequence of peripheral alteration in the leukocyte inflammation-oxidation state.

A New Tailored Nanodroplet Carrier of Astaxanthin Can Improve Its Pharmacokinetic Profile and Antioxidant and Anti-Inflammatory Efficacies.

Astaxanthin (ATX) is a carotenoid nutraceutical with poor bioavailability due to its high lipophilicity. We tested a new tailored nanodroplet capable of solubilizing ATX in an oil-in-water micro-environment (LDS-ATX) for its capacity to improve the ATX pharmacokinetic profile and therapeutic efficacy. We used liquid chromatography tandem mass spectrometry (LC-MS/MS) to profile the pharmacokinetics of ATX and LDS-ATX, superoxide mutase (SOD) activity to determine their antioxidant capacity, protein carbonylation and lipid peroxidation to compare their basal and lipopolysaccharide (LPS)-induced oxidative damage, and ELISA-based detection of IL-2 and IFN-γ to determine their anti-inflammatory capacity. ATX and LDS-ATX corrected only LPS-induced SOD inhibition and oxidative damage. SOD activity was restored only by LDS-ATX in the liver and brain and by both ATX and LDS-ATX in muscle. While in the liver and muscle, LDS-ATX attenuated oxidative damage to proteins and lipids better than ATX; only oxidative damage to lipids was preferably corrected by LDS-ATX in the brain. IL-2 and IFN-γ pro-inflammatory response was corrected by LDS-ATX and not ATX in the liver and brain, but in muscle, the IL-2 response was not corrected and the IFN-γ response was mitigated by both. These results strongly suggest an organ-dependent improvement of ATX bioavailability and efficacy by the LDS-ATX nanoformulation.

3-methyladenine ameliorates acute lung injury by inhibiting oxidative damage and apoptosis.

Background: Acute lung injury (ALI) is a condition characterized by inflammation and oxidative damage. 3-methyladenine (3-MA) has great potential for regulating apoptosis, but its regulatory role in ALI is unknown. Methods: Lipopolysaccharide (LPS)-treated mice and tert-butyl hydroperoxide (TBHP)-treated bronchial epithelial cells were used to simulate in vivo and in vitro ALI models, respectively. In vivo, lung injury was assessed by histopathological analysis and lung injury scoring. The total cell count, protein content, and inflammatory factors in bronchoalveolar lavage fluid (BALF) were examined. The level of apoptosis in lung tissue was assessed through TUNEL staining. In the vitro ALI model, cell viability and levels of reactive oxygen species and apoptosis were assessed. Results: 3-MA pretreatment ameliorated lung injury, including intra-alveolar hemorrhage and inflammatory cell accumulation, both in vitro and in vivo. 3-MA pretreatment also decreased inflammatory factor levels in the BALF. 3-MA pretreatment alleviated oxidative damage, decreased reactive oxygen species levels, and attenuated morphological changes. TUNEL and Annexin V-FITC/PI staining revealed that pretreatment with 3-MA reduced the level of apoptosis. 3-MA pretreatment significantly decreased the expression of caspase-3 and Bax but increased the expression of Bcl-2 in ALI. Mechanistically, 3-MA pretreatment also affected the PKCα/NOX4 and Nrf2 pathways, which decreased the level of apoptosis in ALI. Conclusions: 3-MA pretreatment inhibited inflammation and oxidative damage in ALI and inhibited apoptosis to mitigate ALI in part by inhibiting the PKCα/NOX4 pathway and activating the Nrf2 pathway. Based on these results, 3-MA might be a viable medication to treat with ALI.

Multiomics Analyses Explore the Immunometabolic Interplay in the Liver of White Crucian Carp (Carassius cuvieri) After Aeromonas veronii Challenge.

Aeromonas veronii is one of the predominant pathogenic species that can imperil the survival of farmed fish. However, the interactive networks of immune regulation and metabolic response in A. veronii-infected fish are still unclear. In this investigation, we aimed to explore immunometabolic interplay in white crucian carp (WCC) after the A. veronii challenge. Elevated levels of immune-related genes were observed in various tissues after A. veronii infection, along with the sharp alteration of disease-related enzymatic activities. Besides, decreased levels of antioxidant status were observed in the liver, but most metabolic gene expressions increased dramatically. Multiomics analyses revealed that metabolic products of amino acids, such as formiminoglutamic acid (FIGLU), L-glutamate (L-Glu), and 4-hydroxyhippuric acid, were considered the crucial liver biomarkers in A. veronii-infected WCC. In addition, A. veronii infection may dysregulate endoplasmic reticulum (ER) function to affect the metabolic process of lipids, carbohydrates, and amino acids in the liver of WCC. These results may have a comprehensive implication for understanding immunometabolic response in WCC upon A. veronii infection.