Therapeutic effect of oral insulin-chitosan nanobeads pectin-dextrin shell on streptozotocin-diabetic male albino rats.

The current study inspects the therapeutic effects of orally ingested insulin-loaded chitosan nanobeads (INS-CsNBs) with a pectin-dextrin (PD) coating on streptozotocin (STZ)-induced diabetes in Wistar rats. The study also assessed antioxidant effects in pancreatic tissue homogenate, insulin, C-peptide, and inflammatory markers interleukin-1 beta and interleukin-6 (IL-1ß and IL-6) in serum. Additionally, histopathological and immunohistochemical examination of insulin granules, oxidative stress, nuclear factor kappa B (NF-κB P65), and sirtuin-1 (SIRT-1) protein detection, as well as gene expression of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), B-cell lymphoma 2 (Bcl2), and Bcl-2-associated X protein (Bax) in pancreatic tissue were investigated. After induction of diabetes with STZ, rats were allocated into 6 groups: the normal control (C), the diabetic control (D), and the diabetic groups treated with INS-CsNBs coated with PD shell (50 IU/kg) (NF), free oral insulin (10 IU/kg) (FO), CsNBs-PD shell (50 IU/kg) (NB), and subcutaneous insulin (10 IU/kg) (Sc). The rats were treated daily for four weeks. Treatment of diabetic rats with INS-CsNBs coated with PD shell resulted in a significant improvement in blood glucose levels, elevated antioxidant activities, decreased NF-κB P65, IL-1ß, and IL-6 levels, upregulated Nrf-2 and HO-1, in addition to a marked improvement in the histological architecture and integrity compared to the diabetic group. The effects of oral INS-CsNBs administration were comparable to those of subcutaneous insulin. In conclusion, oral administration of INS-loaded Cs-NBs with a pectin-dextrin shell demonstrated an ameliorative effect on STZ-induced diabetes, avoiding the drawbacks of subcutaneous insulin.

Comprehensive assessment of Zingiber sianginensis: Phytometabolomic analysis and its impact on oxidative stress biomarkers.

In India, ginger is highly valued for cultural and medicinal purposes. Besides traditional uses, ginger has been proven for its efficacy in cancer, chemotherapy-induced nausea, bacterial infections, neuroinflammation, and oxidative stress. This study focuses on Zingiber sianginensis, a rare ginger species in the Siang region of Arunachal Pradesh, India. This study studied pharmacognostical evaluation, phytometabolomics analysis, and its effect on oxidative stress biomarkers. Microscopic and chemical tests were employed for pharmacognostical evaluation, revealing distinctive characteristics of Zingiber sianginensis, such as non-close collateral vascular bundles and unique cork layers. Chemical tests, including the phloroglucinol and hydrochloric acid test, differentiated Zingiber sianginensis from Zingiber officinale Roscoe. Phytometabolomics analysis, using Gas Chromatography-Mass Spectrometry (GC/MS) and Liquid Chromatography-Electrospray Ionisation-Quadrupole Time of Flight-Mass Spectrometry (LC-ESI-QTOF-MS/MS) techniques, identified a diverse range of metabolites in Zingiber sianginensis, including polyphenols, monoterpenoids, diterpenoids, sesquiterpenoids, and organic compounds. The LC-ESI-QTOF-MS/MS analysis revealed 158 compounds, verified through cross-referencing with established databases. Heavy metal analysis by Inductively Coupled Plasma-Mass Spectrometry (ICP-MS) confirmed that Zingiber sianginensis complies with safety standards, showing concentrations of heavy metals within acceptable limits. The isolation and characterization of compounds from Zingiber sianginensis identified natural products such as (R)-(-)- alpha-Curcumene (1), 1-Dehydro-[10]-gingerdione (2), 6-Shogaol (3), and 6-Gingerol (4). Quantification of 6-gingerol revealed that Zingiber sianginensis contains approximately twice the amount compared to Zingiber officinale Roscoe's, suggesting its potential as a source for higher 6-gingerol content. The hydroalcoholic extract of Zingiber sianginensis exhibited antioxidant properties, reducing oxidative stress biomarkers in human dermal fibroblast cells treated with rotenone. Allantoin and 3-bromotyrosine levels significantly decreased, indicating the extract's potential in combating oxidative stress-related disorders. Overall, this comprehensive study provides valuable insights into the pharmacognostical, phytometabolomic, and safety aspects of Zingiber sianginensis, highlighting its potential as a source of bioactive compounds with health benefits.

Serum Biomarkers to Dynamically Predict the Risk of Cardiovascular Events in Patients under Oncologic Therapy. A Multicenter Observational Study.

Background: Serum biomarkers have been investigated as predictive risk factors for cancer-related cardiovascular (CV) risk, but their analysis is limited to their baseline level rather than their overtime change. Besides historically validated causal factors, inflammatory and oxidative stress (OS) related markers seem to be correlated to CV events but this association needs to be further explored. We conducted an observational study to determine the predictive role of the longitudinal changes of commonly used and OS-related biomarkers during the cancer treatment period. Methods: Patients undergoing anticancer therapies, either aged 75+ years old or younger with an increased CV risk according to European Society of Cardiology guidelines, were enrolled. We assessed the predictive value of biomarkers for the onset of CV events at baseline and during therapy using Cox model, Subpopulation Treatment-Effect Pattern Plot (STEPP) method and repeated measures analysis of longitudinal data. Results: From April 2018 to August 2021, 182 subjects were enrolled, of whom 168 were evaluable. Twenty-eight CV events were recorded after a median follow up of 9.2 months (Interquartile range, IQR: 5.1-14.7). Fibrinogen and troponin levels were independent risk factors for CV events. Specifically, patients with higher than the median levels of fibrinogen and troponin at baseline had higher risk compared with patients with values below the medians, hazard ratio (HR) = 3.95, 95% CI, 1.25-12.45 and HR = 2.48, 0.67-9.25, respectively. STEPP analysis applied to Cox model showed that cumulative event-free survival at 18 and 24 months worsened almost linearly as median values of fibrinogen increased. Repeated measure analysis showed an increase over time of D-Dimer (p-interaction event*time = 0.08), systolic (p = 0.07) and diastolic (p = 0.05) blood pressure and a decrease of left ventricular ejection fraction (p = 0.15) for subjects who experienced a CV event. Conclusions: Higher levels of fibrinogen and troponin at baseline and an increase over time of D-Dimer and blood pressure are associated to a higher risk of CV events in patients undergoing anticancer therapies. The role of OS in fibrinogen increase and the longitudinal monitoring of D-dimer and blood pressure levels should be further assessed.

Metabolomic and biochemical disorders reveal the toxicity of environmental microplastics and benzo[a]pyrene in the marine polychaete Hediste diversicolor.

Recently, the abundance of environmental microplastics (MPs) has become a global paramount concern. Besides the danger of MPs for biota due to their tiny size, these minute particles may act as vectors of other pollutants. This study focused on evaluating the toxicity of environmentally relevant concentrations of MPs (10 and 50 mg/kg sediment) and benzo[a]pyrene (B[a]P, 1 µg/kg sediment), alone and in mixture, for 3 and 7 days in marine polychaete Hediste diversicolor, selected as a benthic bioindicator model. The exposure period was sufficient to confirm the bioaccumulation of both contaminants in seaworms, as well as the potential capacity of plastic particles to adsorb and vehiculate the B[a]P. Interestingly, increase of acidic mucus production was observed in seaworm tissues, indicative of a defense response. The activation of oxidative system pathways was demonstrated as a strategy to prevent lipid peroxidation. Furthermore, the comprehensive Nuclear Magnetic Resonance (NMR)-based metabolomics revealed significant disorders in amino acids metabolism, osmoregulatory process, energetic components, and oxidative stress related elements. Overall, these findings proved the possible synergic harmful effect of MPs and B[a]P even in small concentrations, which increases the concern about their long-term presence in marine ecosystems, and consequently their transfer and repercussions on marine fauna.

A short-term exposure to saxitoxin triggers a multitude of deleterious effects in Daphnia magna at levels deemed safe for human health.

Harmful algal blooms and the toxins produced during these events are a human and environmental health concern worldwide. Saxitoxin and its derivatives are potent natural aquatic neurotoxins produced by certain freshwater cyanobacteria and marine algae species during these bloom events. Saxitoxins effects on human health are well studied, however its effects on aquatic biota are still largely unexplored. This work aims at evaluating the effects of a pulse acute exposure (24 h) of the model cladoceran Daphnia magna to 30 µg saxitoxin L-1, which corresponds to the safety guideline established by the World Health Organization (WHO) for these toxins in recreational freshwaters. Saxitoxin effects were assessed through a comprehensive array of biochemical (antioxidant enzymes activity and lipid peroxidation), genotoxicity (alkaline comet assay), neurotoxicity (total cholinesterases activity), behavioral (swimming patterns), physiological (feeding rate and heart rate), and epigenetic (total 5-mC DNA methylation) biomarkers. Exposure resulted in decreased feeding rate, heart rate, total cholinesterases activity and catalase activity. Contrarily, other antioxidant enzymes, namely glutathione-S-transferases and selenium-dependent Glutathione peroxidase had their activity increased, together with lipid peroxidation levels. The enhancement of the antioxidant enzymes was not sufficient to prevent oxidative damage, as underpinned by lipid peroxidation enhancement. Accordingly, average DNA damage level was significantly increased in STX-exposed daphnids. Total DNA 5-mC level was significantly decreased in exposed organisms. Results showed that even a short-term exposure to saxitoxin causes significant effects on critical molecular and cellular pathways and modulates swimming patterns in D. magna individuals. This study highlights sub-lethal effects caused by saxitoxin in D. magna, suggesting that these toxins may represent a marked challenge to their thriving even at a concentration deemed safe for humans by the WHO.

Impact of aged and virgin polyethylene microplastics on multi end-points effects of freshwater fish tissues.

The buildup of plastic waste in aquatic environments presents serious threats to the environment, wildlife, and ultimately to humans. Specifically, microplastics (MPs) ingestion by aquatic animals leads to adverse physiological and toxicological effects. In addition, discarded MPs undergo aging and degradation processes which affect their morphological properties and chemical composition, enhancing the absorption of environmental pollutants. Under this prism, the present research was conducted to investigate and compare the impact of 'aged' versus pristine low-density polyethylene microplastics (PE-MPs) on various toxicity endpoints as biochemical and molecular parameters in the muscle tissue and liver of the freshwater fish species Perca fluviatilis. In parallel, the morphological, physicochemical, and structural changes occurred in "aged" PE-MPs, (after being exposed to UV radiation for 120 days) were studied, significantly illustrating signs of oxidation and crack propagation at the surface of the studied MPs. Fish were exposed to artificial diet reached with virgin and "aged" PE-MPs, sized 100-180 µm, at concentrations of 1 mg/g of dry food for a period of 15-days. Thereafter, liver and muscle tissues were analyzed in relation to multi oxidative parameters. Compared to the control group, the observed changes in the examined fish included increased activities of antioxidant enzymes, as superoxide dismutase, catalase and glutathione reductase, enhanced concentrations of malondialdehyde, protein carbonylation, HSP70 levels, elevated MAPK phosphorylation, induction of ubiquitin-proteins, as well as heightened levels of Bax/Bcl-2 proteins, caspases and differentiated levels of LC3 II/I, SQSTM1/p62. From the studied biomarkers, apoptosis, ubiquitin and hsp70 levels, showed a more sensitive response against the ingested MPs, followed by autophagy, p38MAPK levels, antioxidant enzymes, MDA and carbonylation levels. The effect of "aged" PE-MPs was more pronounced compared to that of the virgin ones. When evaluating the response of all oxidative stress biomarkers across the studied tissues, the liver demonstrates the highest response for the majority of the biomarkers against both virgin and "aged" PE-MPs. These findings strongly indicate that "aged" MPs activate the antioxidant defence mechanisms and impact the cellular well-being of the examined fish species.

Urinary polycyclic aromatic hydrocarbon metabolites in Chinese pregnant women: Concentrations, variability, predictors, and association with oxidative stress biomarkers.

Polycyclic aromatic hydrocarbons (PAHs) are a class of pervasive contaminants having adverse health effects. Urinary monohydroxylated PAHs (OH-PAHs) are commonly employed as biomarkers to estimate PAH exposure levels in humans. However, little is understood about the variability in OH-PAHs among pregnant women across trimesters and their relationship with oxidative stress biomarkers (OSBs). Based on a prospective birth cohort study conducted in Wuhan, China, we selected 644 women who donated (spot) urine samples across different trimesters and measured the urinary concentrations of eight OH-PAHs and three selected OSBs (8-OHG, 8-OHdG, and HNEMA) to explore the relationship between the OH-PAHs and OSBs. Pregnant women were found to be ubiquitously exposed to the PAHs, with detection rates of the OH-PAHs ranging from 86.3% to 100%. 2-Hydroxynaphthalene (2-OH-Nap) had the highest urinary concentrations among the OH-PAHs during the three trimesters (specific gravity-adjusted median values for the first, second, and third trimesters: 1.86, 2.39, and 2.20 ng/mL, respectively). However, low reproducibility of the OH-PAHs was observed across the three trimesters with intraclass correlation coefficients ranged between 0.02 and 0.22. Most urinary OH-PAHs had the highest concentrations at the first trimester and the lowest at the third trimester. Some OH-PAH concentrations were higher in pregnant women with lower educational level [2-hydroxyphenanthrene (2-OH-Phen) and 3-hydroxyphenanthrene (3-OH-Phen)], those who were overweight [2-OH-Nap, 2/3-hydroxyfluorene (2/3-OH-Fluo), 2-OH-Phen, and 4-hydroxyphenanthrene (4-OH-Phen)], those who were unemployed during pregnancy [1-hydroxynaphthalene, 1/9-hydroxyphenanthrene, and 4-OH-Phen], and the samples donated in summer (most OH-PAHs, except for 2-OH-Nap). In multivariable linear mixed-effects model analyses, every OH-PAH was found to be significantly associated with increased levels of the three OSBs. For example, each interquartile range-fold increase in 2/3-OH-Fluo concentration was associated with the largest increase in 8-OHdG (65.4%) and 8-OHG (49.1%), while each interquartile range-fold increase in 3-OH-Phen concentration was associated with the largest increase in HNEMA (76.3%). Weighted quantile sum regression models, which were used to examine the joint effect of OH-PAH mixture on the OSBs, revealed positive associations between the OH-PAH mixture exposure and the OSBs. Specifically, 2/3-OH-Fluo and 2-OH-Nap were the major contributors in the association with oxidative damage of nucleic acids (8-OHdG and 8-OHG), while hydroxyphenanthrenes and 1-hydroxypyrene were the major contributors in the association with oxidative damage of lipid (HNEMA). Further work is required to examine the potential mediating role of oxidative stress in the relationship of adverse health outcomes with elevated PAH exposure among pregnant women.

Influence of acute heat shock on antioxidant defense of tropical fish, Psalidodon bifasciatus.

Psalidodon bifasciatus is a fish species sensitive to physical and chemical changes in water. It serves as a good bioindicator of temperature variations and is utilized in environmental monitoring studies in Brazilian rivers. The objective of this study was to evaluate antioxidant defense biomarkers in the heart, brain, and muscle of P. bifasciatus exposed to a 10 °C thermal increase. P. bifasciatus were collected and divided into a control group (21 °C) and groups subjected to thermal shock (31 °C) for periods of 2, 6, 12, 24, and 48h. Two-way ANOVA indicated that a 10 °C temperature increase caused oxidative stress in P. bifasciatus. This was evidenced by altered levels of lipid peroxidation (LPO), carbonylated proteins (PCO), and glutathione peroxidase (GPx) in the heart, catalase (CAT) and LPO in the brain, and LPO in the muscle. Principal component analysis (PCA) and integrated biomarker response (IBR) analysis indicated that, compared to the heart and muscle, the brain exhibited a greater activation of the antioxidant response. Sensitivity analysis indicated that the muscle was the most sensitive organ, followed by the brain and heart. Our results indicate that the stress response is tissue-specific through the activation of distinct mechanisms. These responses may be associated with the tissue's function as well as its energy demand. As expected, P. bifasciatus showed changes in response to thermal stress, with the brain showing the greatest alteration in antioxidant defenses and the muscle being the most sensitive tissue.

Ameliorative impacts of gamma-aminobutyric acid (GABA) on seedling growth, physiological biomarkers, and gene expression in eight wheat (Triticum aestivum L.) cultivars under salt stress.

Plants spontaneously accumulate γ-aminobutyric acid (GABA), a nonprotein amino acid, in response to various stressors. Nevertheless, there is limited knowledge regarding the precise molecular mechanisms that plants employ to cope with salt stress. The objective of this study was to investigate the impact of GABA on the salt tolerance of eight distinct varieties of bread wheat (Triticum aestivum L.) by examining plant growth rates and physiological and molecular response characteristics. The application of salt stress had a detrimental impact on plant growth markers. Nevertheless, the impact was mitigated by the administration of GABA in comparison to the control treatment. When the cultivars Gemmiza 7, Gemmiza 9, and Gemmiza 12 were exposed to GABA at two distinct salt concentrations, there was a substantial increase in both the leaf chlorophyll content and photosynthetic rate. Both the control wheat cultivars and the plants exposed to salt treatment and GABA treatment showed alterations in stress-related biomarkers and antioxidants. This finding demonstrated that GABA plays a pivotal role in mitigating the impact of salt treatments on wheat cultivars. Among the eight examined kinds of wheat, CV. Gemmiza 7 and CV. Gemmiza 11 exhibited the most significant alterations in the expression of their TaSOS1 genes. CV. Misr 2, CV. Sakha 94, and CV. Sakha 95 exhibited the highest degree of variability in the expression of the NHX1, DHN3, and GR genes, respectively. The application of GABA to wheat plants enhances their ability to cope with salt stress by reducing the presence of reactive oxygen species (ROS) and other stress indicators, regulating stomatal aperture, enhancing photosynthesis, activating antioxidant enzymes, and upregulating genes involved in salt stress tolerance.

Genotoxicity and metabolic changes induced via ingestion of virgin and UV-aged polyethylene microplastics by the freshwater fish Perca fluviatilis.

The present study aims to compare and assess the toxicity induced by aged (irradiated with ultraviolet radiation for 120 days) polyethylene microplastics (PE-MPs) in comparison to virgin (non-irradiated) ones, after feeding the freshwater fish Perca fluviatilis. To this end, MPs mediated genotoxicity was assessed by the investigation of micronucleus nuclear abnormalities frequency in fish blood, and the degree of DNA damage in the liver and muscle tissues, while metabolic alterations were also recorded in both tissues. Results showed that both virgin and aged PE-MPs induced signaling pathways leading to DNA damage and nuclear abnormalities, as well as metabolites changes in all tissues studied. Metabolic changes revealed that the metabolism of nucleic acids, energy, amino acids, and neurotransmitters was more disrupted in the liver and by aged PE-MPs compared to muscles. Fish fed with aged PE-MPs exhibited greater DNA damage, while blood cells of fish fed with virgin PE-MPs seemed to be more vulnerable to nuclear abnormalities in relation to those fed with aged PE-MPs. Moreover, aged PE-MPs induced more acute overall effects on the metabolic profiles of fish tissues, and initiated stronger stress responses, inflammation, and cellular damages in fish tissues in relation to virgin ones. Characterization of both virgin and aged MPs revealed that the latter exhibited lower crystallinity and melting point, more irregular shapes and higher moiety of oxygen and carbonyl groups, which could be attributed for their observed higher toxicity. The research outcomes provide significant insights for advancing toxicological investigations in this field.

Biochemical parameters, oxidative stress biomarkers, and anatomopathological changes in Wistar rats treated with 3'-demethoxy-6-O-demethylisoguaiacin and norisoguaiacin.

Artemisia cina (Ac) is a plant with anthelmintic compounds such as 3'-demethoxy-6-O-demethylisoguaiacin (D) and norisoguaiacin (N). Three major objectives were proposed: (1) To evaluate biochemical parameters in blood (2) to determine the tissue oxidative stress by biomarkers as TBARS and glutathione peroxidase activity, and (3) to evaluate anatomopathological changes in organs such as the brain, liver, kidney, and lung after oral administration of n-hexane extract of Ac and D and N. D and N were administrated following the OECD guides for acute oral toxicity evaluation (Guide 420). Fifty Wistar rats were distributed into ten groups as follows: Group 1 (G1): 4 mg/Kg; G2: 40 mg/Kg; G3: 240 mg/Kg; G4: 1600 mg/Kg of n-hexane extract of Ac. G5: 2 mg/Kg; G6: 20 mg/Kg; G7: 120 mg/Kg; G8: 800 mg/Kg of D and N, G9: water and G10: polyvinylpyrrolidone at 2000 mg/Kg. At 14 days, the rats were euthanized, and the blood, liver, brain, kidney, and lung were taken for biochemical analysis, anatomopathological changes, and TBARS and GSH evaluation. Glucose, cholesterol, and phosphorus were altered. Histopathological analysis showed multifocal neuronal degeneration in the brain (G2). The kidney and lungs had changes in G7. The GSH and TBARS increased in G6 and G7. The TBARS activity was higher in G1 and G2. In conclusion, extract and D and N of Ac did not have damage at therapeutic doses. D, N, and n-hexane extract of A. cina do not cause histopathological damage at pharmaceutical doses. Still, the brain, kidney, and liver are related to biochemical parameters at higher doses. However, compounds are proposed as antioxidant agents.

Effect of antioxidant-rich kindergarten meals on oxidative stress biomarkers in healthy 5-6-year-old children: a randomized controlled trial.

As children spend up to 9 h a day in kindergarten, the main purpose of our study was to evaluate the effect of antioxidant-rich kindergarten meals on oxidative stress biomarkers (OSBs) in healthy children. In the randomized control trial with a follow-up, healthy 5-6-year-old children from six kindergartens were randomly divided into a prototype group (PG, n = 40) and a control group (CG, n = 17). PG followed a 2-week antioxidant-rich kindergarten meal plan (breakfast, lunch, and two snacks), and CG followed their standard kindergarten meal plans. Outside the kindergartens, participants ate as usual. We used a consecutive 7-day dietary record inside and outside the kindergarten and the national dietary assessment tool OPEN to assess the total dietary antioxidant capacity (dTAC) of the consumed foods. Malondialdehyde (MDA), 8-hydroxy-2-deoxyguanosine (8-OHdG), and four F2-isoprostane were measured in fasting urine on days 1 and 15. We also measured total antioxidant power (PAT) and hydroperoxides (d-ROMs) in fasting serum on day 15 and obtained the value of the oxidative stress index (OSI). We used a Welch two-sample t-test and multiple regression analysis to compare the prototype and control groups and a nonparametric Wilcoxon signed rank exact test to compare pre- and post-intervention results in urine. Antioxidant-rich kindergarten meals contributed to a significantly (p < 0.05) higher intake of dTAC in PG participants compared to standard meals in CG participants (8.6 vs. 2.8 mmol/day). We detected a negative correlation between dTAC intake and d-ROMs and between dTAC intake and OSI (r = - 0.29, p = 0.043 and r = - 0.31, p = 0.032, respectively). A significant decrease in urinary 8-iso-15-prostaglandin-F-2 alpha was detected in PG participants between days 1 and 15; however, no other intra-individual significant differences in urinary OSBs were found.  Conclusion: Antioxidant-rich food in kindergarten is warranted due to its potential health-protective effect. Additionally, we present original data on the average levels of urinary and serum OSBs in healthy 5-6-year-old children.  Trial registration: The study was registered at ClinicalTrials.gov, on February 5, 2020 ( https://clinicaltrials.gov/ct2/show/NCT04252105 ). What is Known: • Kindergartens are recognized as promising environments for public health measures. • A diet rich in antioxidants can reduce OSBs and, consequently, the risk of developing NCDs. What is New: • Antioxidant-rich kindergarten diet can ensure a protective intake of dTAC in children. • Original data on serum oxidative stress biomarkers (d-ROMs, PAT, and OSI) and urinary oxidative stress biomarkers (MDA, 8-OHdG, and F2 isoprostanes) in healthy 5-6-year-old children.

Antihypertensive Potential of Japanese Quail (Couturnix Couturnix Japonica) Egg Yolk Oil (QEYO) in Sprague Dawley Rats.

Oils from animal sources have been used for centuries in the management of diseases. This research was conducted to screen the ex vivo and in vivo toxicity of quail egg yolk oil (QEYO) extracts and assess their effects on the management of hypertension in rats. QEYO was extracted using gentle heating (GH) and n-hexane (NHN). The extracts were subjected to toxicity testing using the hen's egg test on chorioallantoic membrane (HET-CAM) and bovine corneal histology test. Acute and sub-chronic toxicity (28 days) were evaluated in rats. Hypertension was induced in rats by administering 80 mg/kg of Nω-L-Arginine Methyl Ester (L-NAME) per day for 28 days. Treatments commenced on the 14th day; Nifedipine at 30 mg/kg and 1 mL of distilled water were administered as positive and negative controls. Blood pressure (BP), lipid profiles, and oxidative stress markers were quantified. No irritation was observed using the HET-CAM test in the egg treated with both extracts. Bovine corneal histology showed no lesions in all treated groups. No signs of toxicity were observed in either acute or sub-chronic toxicity studies. A significant reduction in blood pressure was observed in rats treated with the extracts (p < 0.05). Changes in total cholesterol (TC), triglycerides (TGs), low-density lipoproteins (LDLPs), and high-density lipoproteins (HDLPs) were not significant compared to the control (p > 0.05). Oxidative stress markers (SOD and CAT) increased significantly in the treated groups compared to the control, while the malondialdehyde levels decreased (p < 0.05). QEYO was safe in both ex vivo and in vivo studies and can be said to have the potential to lower blood pressure as well as cardio-protective effects in hypertensive rats. This research provides evidence based on which QEYO could be used safely as an adjuvant therapy in eye drops and cosmetics and can be considered an effective choice for preventing hypertension.

Bioanalysis of Stress Biomarkers through Sensitive HILIC-MS/MS Method: A Stride toward Accurate Quantification of MDA, ACR, and CTA.

Quantifying reactive aldehyde biomarkers, such as malondialdehyde, acrolein, and crotonaldehyde, is the most preferred approach to determine oxidative stress. However, reported analytical methods lack specificity for accurately quantifying these aldehydes as certain methodologies may produce false positive results due to harsh experimental conditions. Thus, in this research work, a novel HILIC-MS/MS method with endogenous histidine derivatization is developed, which proves to have higher specificity and reproducibility in quantifying these aldehydes from the biological matrix. To overcome the reactivity of aldehyde, endogenous histidine is used for its derivatization. The generated adduct is orthogonally characterized by NMR and LC-HRMS. The method employed a hydrophilic HILIC column and multiple reaction monitoring (MRM) to accurately quantify these reactive aldehydes. The developed method is an unequivocal solution for quantifying stress in in vivo and in vitro studies.

NMR Untargeted and HPLC-MS/MS Targeted Metabolomic Approaches for Evaluating Styrene Exposure in the Urine of Shipyard Workers.

Due to its chemical properties, styrene is largely employed in the manufacturing of several products including rubber, polymers and resins, and it is particularly suitable for shipbuilding industry purposes. In this context, the main exposure to styrene occurs in occupational settings. Despite its widespread use, its long-term effects on human health at the occupational level are still unclear. The aim of this pilot study was to evaluate changes in styrene exposure biomarkers related to the metabolic and oxidative stress profiles in the urine of seventeen shipyard workers and seventeen non-exposed subjects. Urinary metabolites were assessed by means of NMR spectroscopy, including mandelic and phenylglyoxylic acids; four oxidative stress biomarkers, namely 8-oxo-7,8-dihydroguanine, 8-oxo-7,8-dihydroguanosine, and 8-oxo-7,8-dihydro-2'-deoxyguanosine and 3-nitrotyrosine, were evaluated via HPLC-MS/MS. The metabolic profiles of exposed workers showed both long- and short-term metabolic responses to styrene exposure compared to non-exposed subjects. From the comparison between non-exposed and before-shift workers, only 8-oxo-7,8-dihydroguanine and 8-oxo-7,8-dihydro-2'-deoxyguanosine levels were significantly different (long term exposure response). At the same time, comparing the non-exposed group with after-shift workers, we observed lower levels of pseudouridine and 1-methylnicotinamide and higher glutamine levels in after-shift workers. The comparison between before-shift and after-shift workers showed that 8-oxo-7,8-dihydroguanine significantly increased after the shift, suggesting its involvement in the exposure to styrene (short-term exposure response). The obtained results, although preliminary, allow us to lay the basis for further human studies aimed at establishing a global understanding of styrene metabolism.

Corrigendum: Remarkable impacts of probiotics supplementation in enhancing of the antioxidant status: results of an umbrella meta-analysis.

[This corrects the article DOI: 10.3389/fnut.2023.1117387.].

Effect of vinpocetine against acrylamide-induced nephrotoxicity in rats.

Vinpocetine (VIN) is a synthetic drug derived from the natural alkaloid vincamine. The antioxidation and anti-inflammation effects of VIN allow it to be used for multiple therapeutic purposes. So, the research aims to discover the possibility of using VIN to improve the nephrotoxicity of acrylamide (ACR). Twenty-four male albino rats were used in the trial: rats in the control group received 0.5 mL of oral saline, rats in the VIN group received an oral dose of VIN (5 mg/kg), rats in the ACR group received an oral dose of ACR (38.27 mg/kg), and rats in the VIN + ACR group received VIN and then ACR 1 h later. Rat blood and kidneys were collected 10 days after the experiment began to assess biochemical parameters and to examine both renal histopathological and immunohistochemistry. The ACR-treated rats showed high levels of serum kidney function biomarkers (creatinine, urea, and uric acid), serum protein biomarkers (total protein, albumin, and globulin), renal kidney injury molecule (KIM)-1, renal malondialdehyde (MDA), and renal caspase-3 immunoexpression. Moreover, ACR lowed both renal superoxide dismutase (SOD) activity and renal glutathione (GSH) level and caused renal histological alterations. While administration of VIN improved serum kidney function biomarkers, serum protein biomarkers, renal KIM-1, renal oxidative stress biomarkers (MDA, SOD, and GSH), renal caspase-3 immunoexpression, and renal histological alterations induced by ACR. The study confirmed the ability of VIN to reduce the nephrotoxic effects of ACR, which was evident through the results of biochemical parameters and histological and immunohistochemical examinations of the kidney tissues.

Dehorning Does Not Alter the Stress Response in Southern White Rhinoceroses (Ceratotherium simum simum) during Transport: A Preliminary Investigation.

Translocation and dehorning are common and important practices for rhinoceros management and conservation. It is not known if dehorning causes a stress response or negatively affects rhinoceroses during transport. Twenty-three subadult wild Southern white rhinoceros (Ceratotherium simum simum) bulls were immobilized and translocated >280 km for population management reasons. Ten animals were dehorned at capture, and 13 animals were transported without dehorning. For transport, five dehorned and six nondehorned rhinoceroses were sedated with azaperone (62.38±9.54 µg/kg) and five dehorned and seven nondehorned rhinoceroses with midazolam (64.61±9.28 µg/kg). Blood samples were collected at capture, start of transport, and after 6 h of transport. Measurements included 10 physiologic variables: hematocrit, total serum protein, creatine kinase (CK), aspartate aminotransferase, gamma-glutamyl transferase (GGT), creatinine, urea, cholesterol, ß-hydroxybutyrate, and glucose; and four stress response variables: cortisol, epinephrine, neutrophil-to-lymphocyte ratio, and leukocyte coping capacity. Using a linear mixed model, CK and GGT were higher in dehorned compared with nondehorned rhinoceroses. There were no significant differences in the other variables between the two groups. The likely cause of these differences is that dehorned animals spent more time in the crate before the start of transport than nondehorned rhinoceroses (3:11±0:54 h vs. 1:12±0:56 h, P<0.001). These results indicate that dehorning does not negatively alter the white rhinoceros' physiologic and stress responses during translocation, supporting its use for antipoaching measures.

Allostatic load in early pregnancy and sleep-disordered breathing.

OBJECTIVES: To assess the association between allostatic load in early pregnancy and sleep-disordered breathing (SDB) during pregnancy. METHODS: High allostatic load in the first trimester was defined as ≥ 4 of 12 biomarkers (systolic blood pressure, diastolic blood pressure, body mass index, cholesterol, low-density lipoprotein, high-density lipoprotein, high sensitivity C-reactive protein, triglycerides, insulin, glucose, creatinine, and albumin) in the unfavorable quartile. SDB was objectively measured using the Embletta-Gold device and operationalized as "SDB ever" in early (6-15 weeks) or mid-pregnancy (22-31 weeks); SDB at each time point was analyzed as secondary outcomes. Multivariable logistic regression was used to test the association between high allostatic load and SDB, adjusted for confounders. Moderation and sensitivity analyses were conducted to assess the role of allostatic load in racial disparities of SDB and obesity affected the relationship between allostatic load and SDB. RESULTS: High allostatic load was present in 35.0% of the nuMoM2b cohort. The prevalence of SDB ever occurred among 8.3% during pregnancy. After adjustment, allostatic load remained significantly associated with SDB ever (aOR= 5.3; 3.6-7.9), in early-pregnancy (aOR= 7.0; 3.8-12.8), and in mid-pregnancy (aOR= 5.8; 3.7-9.1). The association between allostatic load and SDB was not significantly different for people with and without obesity. After excluding BMI from the allostatic load score, the association decreased in magnitude (aOR= 2.6; 1.8-3.9). CONCLUSION: The association between allostatic load and SDB was independent of confounders including BMI. The complex and likely bidirectional relationship between chronic stress and SDB deserves further study in reducing SDB.

Recent Advances in Electrochemical Biosensors Targeting Stress Markers.

INTRODUCTION: When the body experiences a change in its internal environment due to factors such as mood (euphoria, stress) and illness, it releases biomarkers in large quantities. These biomarkers are used for detecting a disease at its early stages. This involves the detection of insufficient quantities of biocomponents, which can be done by using nanomaterials, conventional materials, and biotechnology; thus, scientists can increase the sensitivity of electrochemical sensors. According to studies conducted in this area, electrochemical sensors have shown promise as a diagnostic tool due to their ability to identify and pinpoint illness biomarkers. The present review article was compiled to gather the latest information on electrochemical biosensors targeting stress markers. MATERIALS AND METHODS: The authors searched scholarly databases like ScienceDirect, Pubmed, Medline, and Scopus for information on electrochemical biosensors targeting stress markers. RESULTS: In this article, we looked at the recent developments in electrochemical sensors for stress monitoring. Because of advances in nanomaterial and biomolecule processes, electrochemical biosensors have been developed with the sensitivity to detect several biomarkers in real-time in therapeutically relevant materials. CONCLUSION: This biomarker sensor strategy can analyze various biofluids (sweat, plasma, urine, and saliva).