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.

Azilsartan as a preventive agent against cyclophosphamide-induced testicular injury in male rats.

Cyclophosphamide (CP) is a popular cancer treatment; however, despite its efficacy, it is known to cause harm to the testicles. To mitigate the reproductive damage caused by CP in male rats, we examined the protective effect of azilsartan (AZ) on CP-induced testicular damage. Thirty Sprague-Dawley male rats were equally divided into three groups: normal control group: received 0.5% CMC suspension for 13 days; induction group: received a single dose of 200 mg/kg of CP on day 6 by intraperitoneal (IP) injection, azilsartan group: received azilsartan (4 mg/kg) orally for 5 days followed by a single dose of 200 mg/kg of (CP) on day 6 by IP injection, then azilsartan administered again for 7 days. Animals were sacrificed on day 14, and sperm characteristics, testosterone levels, and testicular histopathology were evaluated. Induction with CP caused a significant reduction in median value compared to normal control in sperm count (12.0 vs. 22.0 × 106/mm3), sperm motility (30 vs. 90%), abnormal sperm (30.32 vs. 14.43%), dead sperm count (32.43 vs. 10.49 × 106/mm3), DNA fragmentation (21.57 vs. 5.49%); meanwhile, azilsartan prevent these effects on median sperm count (17.0 × 106/mm3), sperm motility (70.0%), abnormal sperm (23.19%), dead sperm count (26.17 × 106/mm3), DNA fragmentation (13.81%), and improved plasmatic testosterone levels compared to the CP group and prevented histopathological alterations of the testes. Azilsartan's mitigation of CP's effects suggests it can prevent male rats' reproductive damage caused by CP. One possible explanation for AZ's protective effects is that it inhibits lipid peroxidation and has antioxidant properties.

Embryonic thermal challenge is associated with increased stressor resiliency later in life: Molecular and morphological mechanisms in the small intestine.

Developing chick embryos that are subjected to increased incubation temperature are more stressor-resilient later in life, but the underlying process is poorly understood. The potential mechanism may involve changes in small intestine function. In this study, we determined behavioral, morphological, and molecular effects of increased embryonic incubation temperatures and post-hatch heat challenge in order to understand how embryonic heat conditioning (EHC) affects gut function. At 4 days post-hatch, duodenum, jejunum, and ileum samples were collected at 0, 2, and 12 h relative to the start of heat challenge. In EHC chicks, we found that markers of heat and oxidative stress were generally lower while those of nutrient transport and antioxidants were higher. Temporally, gene expression changes in response to the heat challenge were similar in control and EHC chicks for markers of heat and oxidative stress. Crypt depth was greater in control than EHC chicks at 2 h post-challenge, and the villus height to crypt depth ratio increased from 2 to 12 h in both control and EHC chicks. Collectively, these results suggest that EHC chicks might be more energetically efficient at coping with thermal challenge, preferentially allocating nutrients to other tissues while protecting the mucosal layer from oxidative damage. These results provide targets for future studies aimed at understanding the molecular mechanisms underlying effects of embryonic heat exposure on intestinal function and stressor resiliency later in life.

An Insight of Plant Source, Toxicological Profile, and Pharmacological Activities of Iridoid Loganic Acid: A Comprehensive Review.

This study evaluates the pharmacological effects of iridoid glucoside loganic acid, a plant constituent with diverse properties, based on literature, and explores the underlying cellular mechanisms for treating several ailments. Data were collected from reliable electronic databases, including PubMed, Scopus, Web of Science, and Google Scholar, etc. The results demonstrated the anti-inflammatory, anti-oxidant, and other protective effects of loganic acid on metabolic diseases and disorders such as atherosclerosis, diabetes, and obesity, in addition to its osteoprotective and anticancer properties. The antioxidant activity of loganic acid demonstrates its capacity to protect cells from oxidative damage and mitigates inflammation by reducing the activity of inflammatory cytokines involving TNF-α and IL-6, substantially upregulating the expression of PPAR-γ/α, and decreasing the clinical signs of inflammation-related conditions related to hypertriglyceridemia and atherosclerosis. Meanwhile, loganic acid inhibits bone loss, exhibits osteoprotective properties by increasing mRNA expression levels of bone synthesizing genes such as Alpl, Bglap, and Sp7, and significantly increases osteoblastic proliferation in preosteoblast cells. Loganic acid is an anti-metastatic drug that reduces MnSOD expression, inhibits EMT and metastasis, and prevents cellular migration, proliferation, and invasion in hepatocellular carcinoma cells. However, additional clinical trials are required to assess its safety, efficacy, and human dose.

Ningxiang Pig-Derived Parabacteroides distasonis HNAU0205 Alleviates ETEC-Induced Intestinal Apoptosis, Oxidative Damage, and Inflammation in Piglets.

Weaning is a critical stage in the growth and development of piglets, often inducing stress reactions. This study aims to investigate the effects of Parabacteroides distasonis (PBd) derived from Ningxiang pigs on growth performance, intestinal apoptosis, oxidative damage, and inflammation in ETEC-challenged weaned piglets. A total of 22 Duroc × Landrace × Yorkshire (DLY) piglets, 24 days old with similar body weights, were randomly divided into three groups: Control (n = 7), ETEC (n = 7), and PBd + ETEC (n = 8). The results show that, compared to the Control group, ETEC challenge led to decreased growth performance, reduced villus height in the duodenum and jejunum, increased crypt depth in the duodenum, a decreased villus-height-to-crypt-depth ratio, increased expression of apoptosis-related genes (Caspase-8 and Caspase-9), increased expression of oxidative damage-related genes (Nrf2, GSH-PX, mTOR, and Beclin1), increased expression of inflammation-related genes (Myd88, P65, TNF-α, and IL-6), and reduced the contents of SCFAs in the colonic chyme (acetate, propionate, butyrate, valerate, and total SCFAs). Compared to the ETEC group, the PBd + ETEC group alleviated the reduction in growth performance, mitigated intestinal morphological damage, and reduced the expression of the aforementioned apoptosis, oxidative damage, and inflammation-related genes with the increase in SCFAs. In conclusion, PBd derived from Ningxiang pigs effectively reduces ETEC-induced intestinal damage in weaned piglets, improves intestinal health, and increases the content of SCFAs in the colonic chyme, thereby enhancing growth performance.

Effects of environmental concentrations of sulfamethoxazole on Skeletonema costatum and Phaeodactylum tricornutum: Insights into growth, oxidative stress, biochemical components, ultrastructure, and transcriptome.

This study aimed to assess the ecological risks posed by sulfamethoxazole (SMX) at environmentally relevant concentrations. Specifically, its effects on the growth and biochemical components (total protein, total lipid, and total carbohydrate) of two marine microalgae species, namely Skeletonema costatum (S. costatum) and Phaeodactylum tricornutum (P. tricornutum), were investigated. Our findings revealed that concentrations of SMX below 150 ng/L stimulated the growth of both microalgae. Conversely, at higher concentrations, SMX inhibited their growth while promoting the synthesis of photosynthetic pigments, total protein, total lipid, and total carbohydrate (P < 0.05). Transmission electron microscope (TEM) observations demonstrated significant alterations in the ultrastructure of algal cells exposed to SMX, including nuclear marginalization, increased chloroplast volume, and heightened vacuolation. In addition, when SMX was lower than 250 ng/L, there was no oxidative damage in two microalgae cells. However, when SMX was higher than 250 ng/L, the antioxidant defense system of algal cells was activated to varying degrees, and the level of malondialdehyde (MDA) increased, indicating that algae cells were damaged by oxidation. From the molecular level, environmental concentration of SMX can induce microalgae cells to produce more energy substances, but there are almost no other adverse effects, indicating that the low level of SMX at the actual exposure level was unlikely to threaten P. tricornutum, but a higher concentration can significantly reduce its genetic products, which can affect the changes of its cell structure and damage P. tricornutum to some extent. Therefore, environmental concentration of SMX still has certain potential risks to microalgae. These outcomes improved current understanding of the potential ecological risks associated with SMX in marine environments.

Mechanistic insights into cadmium exacerbating 2-Ethylhexyl diphenyl phosphate-induced human keratinocyte toxicity: Oxidative damage, cell apoptosis, and tight junction disruption.

Organophosphate flame retardants 2-ethylhexyldiphenyl phosphate (EHDPP) and cadmium (Cd) are ubiquitous in environmental matrices, and dermal absorption is a major human exposure pathway. However, their detrimental effects on the human epidermis remain largely unknown. In this study, human keratinocytes (HaCaT cells) were employed to examine the toxicity and underlying mechanisms of co-exposure to EHDPP and Cd. Their influence on cell morphology and viability, oxidative damage, apoptosis, and tight junction were determined. The results showed that co-exposure decreased cell viability by >40 %, induced a higher level of oxidative damage by increasing the generation of reactive oxygen species (1.3 folds) and inhibited CAT (79 %) and GPX (90 %) activities. Moreover, Cd exacerbated EHDPP-induced mitochondrial disorder and cellular apoptosis, which was evidenced by a reduction in mitochondrial membrane potential and an elevation of cyt-c and Caspase-3 mRNA expression. In addition, greater loss of ZO-1 immunoreactivity at cellular boundaries was observed after co-exposure, indicating skin epithelial barrier function disruption, which may increase the human bioavailability of contaminants via the dermal absorption pathway. Taken together, oxidative damage, cell apoptosis, and tight junction disruption played a crucial role in EHDPP + Cd triggered cytotoxicity in HaCaT cells. The detrimental effects of EHDPP + Cd co-exposure were greater than individual exposure, suggesting the current health risk assessment or adverse effects evaluation of individual exposure may underestimate their perniciousness. Our data imply the importance of considering the combined exposure to accurately assess their health implication.

Ameliorating the detrimental effects of chromium in wheat by silicon nanoparticles and its enriched biochar.

Increased anthropogenic activities over the last decades have led to a gradual increase in chromium (Cr) content in the soil, which, due to its high mobility in soil, makes Cr accumulation in plants a serious threat to the health of animals and humans. The present study investigated the ameliorative effect of foliar-applied Si nanoparticles (SiF) and soil-applied SiNPs enriched biochar (SiBc) on the growth of wheat in Cr-polluted soil (CPS). Two levels of CPS were prepared, including 12.5 % and 25 % by adding Cr-polluted wastewater in the soil as soil 1 (S1) and soil 2 (S2), respectively for the pot experiment with a duration of 40 days. Cr stress significantly reduced wheat growth, however, combined application of SiF and SiBc improved root and shoot biomass production under Cr stress by (i) reducing Cr accumulation, (ii) increasing activities of antioxidant enzymes (ascorbate peroxidase and catalase), and (iii) increasing protein and total phenolic contents in both root and shoot respectively. Nonetheless, separate applications of SiF and SiBc effectively reduced Cr toxicity in shoot and root respectively, indicating a tissue-specific regulation of wheat growth under Cr. Later, the Langmuir and Freundlich adsorption isotherm analysis showed a maximum soil Cr adsorption capacity ∼ Q(max) of 40.6 mg g-1 and 59 mg g-1 at S1 and S2 respectively, while the life cycle impact assessment showed scores of -1 mg kg-1 and -211 mg kg-1 for Cr in agricultural soil and - 0.184 and - 38.7 for human health at S1 and S2 respectively in response to combined SiF + SiBC application, thus indicating the environment implication of Si nanoparticles and its biochar in ameliorating Cr toxicity in different environmental perspectives.

Mitochondrial DNA copy number and risk of papillary thyroid carcinoma.

BACKGROUND: Mitochondrial DNA (mtDNA) copy number is associated with tumor activity and carcinogenesis. This study was undertaken to investigate mtDNA copy number in papillary thyroid cancer (PTC) tissues and to evaluate the risk of PTC development. The clinicopathological features of patients and mtDNA copy number were correlated. The value of mtDNA copy number was evaluated as a biomarker for PTC. METHOD: DNA was extracted from 105 PTC tissues and 67 control thyroid tissues, and mtDNA copy number mtDNA oxidative damage were determined using qPCR techniques. RESULTS: Overall, the relative mtDNA copy number was significantly higher in PTC patients (p < 0.001). The risk of developing PTC increased significantly across the tertiles of mtDNA copy number (p trend < 0.001). The higher the mtDNA copy number tertile, the greater the risk of developing PTC. Patients with follicular variants had an odds ratio of 2.09 (95% CI: 1.78-2.44) compared to those with classical variants (p < 0.001). The level of mtDNA oxidative damage in PTC was significantly elevated compared to controls (p < 0.001). The ROC analysis of mtDNA copy number indicated an area under the curve (AUC) of 77.7% (95% CI: 0.71 to 0.85, p < 0.001) for the ability of mtDNA copy number z-scores in differentiate between PTC and controls. CONCLUSION: Our results indicated that the augmentation of mtDNA content plays a significant role during the initiation of thyroid cancer, and it might represent a potential biomarker for predicting the risk of PTC.

Alleviating effect of methionine on intestinal mucosal injury induced by heat stress.

Climate change is an increasing concern of stakeholders worldwide. The intestine is severely impacted by the heat stress. This study aimed to investigate the alleviating effects of methionine on the intestinal damage induced by heat stress in mice. The mice were divided into four groups: control group (C), methionine deficiency group (MD), methionine + heat stress group (MH), and methionine deficiency + heat stress group (MDH). Histopathological techniques, PAS-Alcian blue staining, immunohistochemistry method, biochemical quantification method, ELISA, and micro method were used to study the changes in the intestinal mucosal morphology, the number of goblet cells, the expression of tight junction proteins, the peroxide product contents and antioxidant enzyme activities, the intestinal mucosal damage, the content of immunoglobulins and HSP70, the activity of Na+/K+-ATPase. The results showed that methionine can improve intestinal mucosal morphology (increase the villi height, V/C value, and muscle layer thickness, decrease crypt depth), increase the expression of tight junction proteins (Claudin-1, Occludin, ZO-1) and the content of DAO, decrease the content of intestinal mucosa damage markers (ET, FABP2) and peroxidation products (MDA), increase the activity of antioxidant enzymes (GR, GSH-Px, SOD), the number of goblet cells, the contents of immunoglobulins (sIgA, IgA, IgG, IgM) and stress protein (HSP70), and the activity of Na+/K+-ATPase. It is suggested that methionine can alleviate intestinal damage in heat-stressed mice.

Revealing the exceptional antioxidant activity of phosphorylated polysaccharides from medicinal Abrus cantoniensis Hance.

Abrus cantoniensis Polysaccharides (ACP) exhibit antioxidant activity and immune-regulatory functions. Abrus cantoniensis Hance widely distributed in the Guangdong and Guangxi regions of China. In this study, this research investigated the impact of phosphorylation modification on the biological activity of ACP, aiming to provide theoretical insights for its development. This research modified ACP through phosphorylation and evaluated changes in its in vitro antioxidant capacity, including free radical scavenging and resistance to cellular oxidative damage. Additionally, this research administered both native ACP and phosphorylated ACP (P-ACP) to mice to assess their protective effects against acute ethanol-induced oxidative injury. This research explored whether these effects were mediated through the Keap1-Nrf2 signaling pathway and their influence on gut microbiota. Results revealed that phosphorylation significantly enhanced ACP's antioxidant capacity and protective effects (p < 0.05). P-ACP improved mice resistance to acute oxidative injury, mitigating the adverse effects of 50 % ethanol (p < 0.05). Moreover, both ACP and P-ACP are involved in modulating the expression of the Keap1-Nrf2 signaling pathway and, to some extent, alter the composition of the gut microbiota in mice. In summary, phosphorylation modification effectively enhances ACP's antioxidant capacity and provides better protection against acute oxidative injury in mice.

Comparative evaluation of oxidative and biochemical parameters of red cell concentrates (RCCs) prepared from G6PD deficient donors and healthy donors during RCC storage.

INTRODUCTION: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common inherited enzyme disorder in red blood cell (RBC). Due to the importance of G6PD enzyme as an antioxidant in RBC, we tried to investigate the oxidative damage in red cell concentrates (RCCs) prepared from donors with G6PD enzyme deficiency in comparison with healthy donors. MATERIAL METHOD: This cross-sectional study was conducted on 20 male donors. Ten of the donors had G6PD deficiency (as a case) and the others had normal enzyme activity (as a control). Biochemical and oxidative damage parameters were examined in RCCs prepared from two groups on days 0, 7, 14, 21, 28 and 35 of RCCs storage; data comparison was analyzed by SPSS statistical software. RESULTS: According to the result, lactate concentration increased significantly from the 7th day to the 35th day of RCC storage in G6PD-deficient donors compared to the control (P<0.05). In addition, malondialdehyde (MDA) concentration in G6PD-deficient RCC showed a significant increase compared to the control in all days of storage (P<0.05). Among the hematological parameters, mean corpuscular volume (MCV) and mean cell hemoglobin (MCH) increased significantly in all days of RCC storage in G6PD-deficient donors compared to the control (P<0.05). CONCLUSION: Our study showed that oxidative changes in G6PD-deficient donors were significantly increased compared to the healthy donors, which probably leads to RCC storage lesion and an increase in blood transfusion complications. Due to the high prevalence of G6PD enzyme deficiency in pandemic areas, it seems that enzyme screening should be included in donor screening programs.

Vascular endothelial cells of Mongolian gerbils are resistant to cholesterol-induced mitochondrial dysfunction and oxidative damage.

Atherosclerosis is essentially the leading factor behind occurrences of cardiovascular diseases (CVDs)-associated incidents, while mitochondrial dysfunction is also the main cause of atherosclerosis. The present study conducted a comparative analysis of mitochondrial function-related indicators in cholesterol-induced vascular endothelial cells (VECs) from Mongolian gerbils, Sprague-Dawley (SD) rats and humans. It reported that the inhibitory effect of cholesterol treatment on the viability of Mongolian gerbil VECs was markedly lower than the other two types of VECs at the same concentration. Following cholesterol treatment, mitochondrial DNA copy numbers, reactive oxygen species level, calcium concentration and mitochondrial membrane potential of Mongolian gerbil VECs did not change markedly. These results suggested that the function of mitochondria in the VECs of Mongolian gerbil is normal. Additionally, cholesterol treatment also did not alter the levels of superoxide dismutase, glutathione peroxidase, ATP, NADH-CoQ reductase and cytochrome c oxidase in Mongolian gerbil VECs. It was hypothesized that the VECs of Mongolian gerbils have certain resistance to oxidative damage induced by cholesterol. In brief, the present study demonstrated that VECs of Mongolian gerbils are resistant to cholesterol-induced mitochondrial dysfunction and oxidative damage. The aforementioned findings establish a theoretical foundation for the advancement of innovative strategies in the prevention and treatment of atherosclerosis.

Oxylipin profiling analyses reveal that ω-3 PUFA is more susceptible to lipid oxidation in sheep testis under oxidative stress.

Reactive oxygen species causes oxidative stress, which oxidizes polyunsaturated fatty acids (PUFAs) to form oxidative metabolites. Sertoli cell is an important cellular metabolism of PUFA in testicular cells, and it regulates the testis development and spermatogenesis. However, the oxylipins generated in testes with different developmental statuses are lacking. In this study, twelve 6-month-old Hu sheep were selected and divided into large testicular group (L) and the small testicular group (S) (n=6). UPLC-MS/MS was conducted to screen oxylipins in the testis, and the total oxylipin and ω-3 PUFA-derived oxylipin contents in the S group were higher. A total of 20 differential oxylipins between the two groups were screened. Among them, the contents of ω-3 PUFA, DHA-derived oxylipins were increased in the S group. The arachidonic acid-derived oxylipin was lower in the S group. The mRNA expression levels of genes related to oxylipin regulation (AKR1B1, PTGER2, and PTGDS) were higher in the S group (P < 0.05). In vitro, 200 µM α-linolenic acid alleviated oxidative stress damage to Sertoli cells and improved cell viability by increasing the superoxide dismutase contents and mRNA expression levels of GPX4 and Bcl2. These results indicate that ω-3 PUFA is more susceptible to lipid oxidation in the S group under oxidative stress, which might alleviate the damage of oxidative stress to testis. Moreover, ALA could stimulate the proliferation of Sertoli cells by increasing the capacity of antioxidants. This work may provide a theoretical basis for further studies on the antioxidant properties of the testis for Hu sheep.

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.

Metabolic perturbation and oxidative damage induced by tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) and tris(2-ethylhexyl) phosphate (TEHP) on Escherichia coli through integrative analyses of metabolome.

Organophosphate esters (OPEs) are one of the emerging environmental threats, causing the hazard to ecosystem safety and human health. Yet, the toxic effects and metabolic response mechanism after Escherichia coli (E.coli) exposed to TDCIPP and TEHP is inconclusive. Herein, the levels of SOD and CAT were elevated in a concentration-dependent manner, accompanied with the increase of MDA contents, signifying the activation of antioxidant response and occurrence of lipid peroxidation. Oxidative damage mediated by excessive accumulation of ROS decreased membrane potential and inhibited membrane protein synthesis, causing membrane protein dysfunction. Integrative analyses of GC-MS and LC-MS based metabolomics evinced that significant perturbation to the carbohydrate metabolism, nucleotide metabolism, lipids metabolism, amino acid metabolism, organic acids metabolism were induced following exposure to TDCIPP and TEHP in E.coli, resulting in metabolic reprogramming. Additionally, metabolites including PE(16:1(5Z)/15:0), PA(17:0/15:1(9Z)), PC(20:2(11Z,14Z)/12:0), LysoPC(18:3(6Z,9Z,12Z)/0:0) were significantly upregulated, manifesting that cell membrane protective molecule was afforded by these differential metabolites to improve permeability and fluidity. Overall, current findings generate new insights into the molecular toxicity mechanism by which E.coli respond to TDCIPP and TEHP stress and supply valuable information for potential ecological risks of OPEs on aquatic ecosystems.

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.

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.