Oxidative Stress Response Research Articles

Protecting effects of 4-octyl itaconate on neonatal hypoxic-ischemic encephalopathy via Nrf2 pathway in astrocytes

BackgroundNeonatal hypoxic-ischemic encephalopathy (HIE) is one of the most common neurological problems occurring in the perinatal period. However, there still is not a promising approach to reduce long-term neurodevelopmental outcomes of HIE. Recently, itaconate has been found to exhibit anti-oxidative and anti-inflammatory effects. However, the therapeutic efficacy of itaconate in HIE remains inconclusive. Therefore, this study attempts to explore the pathophysiological mechanisms of oxidative stress and inflammatory responses in HIE as well as the potential therapeutic role of a derivative of itaconate, 4-octyl itaconate (4OI).MethodsWe used 7-day-old mice to induce hypoxic-ischemic (HI) model by right common carotid artery ligation followed by 1 h of hypoxia. Behavioral experiments including the Y-maze and novel object recognition test were performed on HI mice at P60 to evaluate long-term neurodevelopmental outcomes. We employed an approach combining non-targeted metabolomics with transcriptomics to screen alterations in metabolic profiles and gene expression in the hippocampal tissue of the mice at 8 h after hypoxia. Immunofluorescence staining and RT-PCR were used to evaluate the pathological changes in brain tissue cells and the expression of mRNA and proteins. 4OI was intraperitoneally injected into HI model mice to assess its anti-inflammatory and antioxidant effects. BV2 and C8D1A cells were cultured in vitro to study the effect of 4OI on the expression and nuclear translocation of Nrf2. We also used Nrf2-siRNA to further validate 4OI-induced Nrf2 pathway in astrocytes.ResultsWe found that in the acute phase of HI, there was an accumulation of pyruvate and lactate in the hippocampal tissue, accompanied by oxidative stress and pro-inflammatory, as well as increased expression of antioxidative stress and anti-inflammatory genes. Treatment of 4OI could inhibit activation and proliferation of microglial cells and astrocytes, reduce neuronal death and relieve cognitive dysfunction in HI mice. Furthermore, 4OI enhanced nuclear factor erythroid-2-related factor (Nfe2l2; Nrf2) expression and nuclear translocation in astrocytes, reduced pro-inflammatory cytokine production, and increased antioxidant enzyme expression.ConclusionOur study demonstrates that 4OI has a potential therapeutic effect on neuronal damage and cognitive deficits in HIE, potentially through the modulation of inflammation and oxidative stress pathways by Nrf2 in astrocytes.

Effects of a Tai Chi rehabilitation program implemented using a hybrid online and offline mode on oxidative stress and inflammatory responses in patients with coronary heart disease: a randomized controlled trial

BackgroundCoronary heart disease (CHD) is the leading cause of death in both developed and many developing countries. Exercise training is a fundamental component of cardiac rehabilitation programs for patients with CHD. This study aims to investigate the effects of a Tai Chi rehabilitation program, which is provided through a hybrid online and offline mode, on oxidative stress and inflammatory responses in patients with CHD.MethodsA total of 34 patients with coronary heart disease were randomly assigned to two groups: an experiment group (n = 14, age 62.07 ± 9.076 years) and a control group (n = 20, age 61.90 ± 9.700 years). The experiment group underwent a 12-week Tai Chi cardiac rehabilitation program (TCCRP), while the control group followed a conventional exercise rehabilitation program (CERP) consisting of 1-h sessions, 3 times per week, for a total of 36 sessions. Participants were studied at baseline and post-intervention. The main assessments include the levels of Malondialdehyde (MDA), Superoxide dismutase (SOD), Tumor necrosis factor (TNF-α) and Interleukin-10 (IL − 10) in blood samples. Pearson correlation analysis was used, and the differences between the two groups were subsequently tested using two-way repeated ANOVA. Statistical significance was defined as a two-sided p-value of <0.05.ResultsThe key finding of the study reveals that MDA was significantly reduced by 1.027 nmoL/mL. Additionally, the TCCRP showed significant improvements in SOD and IL-10, with values of 10.110 U/mL and 2.441 pg./mL, respectively. Notably, a significant positive correlation was found between SOD and IL-10 (r = 0.689, p = 0.006), while MDA showed a significant positive correlation with TNF-a (r = 0.542, p = 0.045). In contrast, the ECRP group only showed a significant improvement in SOD.ConclusionThe study conducted a 12-week program on TCCRP, which utilized a hybrid online and offline model for individuals with coronary heart disease. The program showed promising results in alleviating oxidative stress and inflammation, possibly by regulating the balance between oxidative and antioxidative factors, as well as pro-inflammatory and anti-inflammatory factors.

Comparative transcriptomics revealed neurodevelopmental impairments and ferroptosis induced by extremely small iron oxide nanoparticles

Iron oxide nanoparticles are a type of nanomaterial composed of iron oxide (Fe3O4 or Fe2O3) and have a wide range of applications in magnetic resonance imaging. Compared to iron oxide nanoparticles, extremely small iron oxide nanoparticles (ESIONPs) (∼3 nm in diameter) can improve the imaging performance due to a smaller size. However, there are currently no reports on the potential toxic effects of ESIONPs on the human body. In this study, we applied ESIONPs to a zebrafish model and performed weighted gene co-expression network analysis (WGCNA) on differentially expressed genes (DEGs) in zebrafish embryos of 48 hpf, 72 hpf, 96 hpf, and 120 hpf using RNA-seq technology. The key hub genes related to neurotoxicity and ferroptosis were identified, and further experiments also demonstrated that ESIONPs impaired the neuronal and muscle development of zebrafish, and induced ferroptosis, leading to oxidative stress, cell apoptosis, and inflammatory response. Here, for the first time, we analyzed the potential toxic effects of ESIONPs through WGCNA. Our studies indicate that ESIONPs might have neurotoxicity and could induce ferroptosis, while abnormal accumulation of iron ions might increase the risk of early degenerative neurological diseases.

Neem Leaf Extract Exhibits Anti-Aging and Antioxidant Effects from Yeast to Human Cells.

Neem leaves have long been used in traditional medicine for promoting longevity. However, the precise mechanisms underlying their anti-aging effects remain elusive. In this study, we investigated the impact of neem leaf extract (NLE) extracted from a 50% ethanol solution on the chronological lifespan of Saccharomyces cerevisiae, revealing an extension in lifespan, heightened oxidative stress resistance, and a reduction in reactive oxygen species. To discern the active compounds in NLE, LC/MS and the GNPS platform were employed. The majority of identified active compounds were found to be flavonoids. Subsequently, compound-target pharmacological networks were constructed using the STP and STITCH platforms for both S. cerevisiae and Homo sapiens. GOMF and KEGG enrichment analyses of the predicted targets revealed that "oxidoreductase activity" was among the top enriched terms in both yeast and human cells. These suggested a potential regulation of oxidative stress response (OSR) by NLE. RNA-seq analysis of NLE-treated yeast corroborated the anti-oxidative effect, with "oxidoreductase activity" and "oxidation-reduction process" ranking high in enriched GO terms. Notably, CTT1, encoding catalase, emerged as the most significantly up-regulated gene within the "oxidoreductase activity" cluster. In a ctt1 null mutant, the enhanced oxidative stress resistance and extended lifespan induced by NLE were nullified. For human cells, NLE pretreatment demonstrated a decrease in reactive oxygen species levels and senescence-associated β-galactosidase activity in HeLa cells, indicative of anti-aging and anti-oxidative effects. This study unveils the anti-aging and anti-oxidative properties of NLE while delving into their mechanisms, providing novel insights for pharmacological interventions in aging using phytochemicals.

Revealing the pharmacological mechanisms of nao-an dropping pill in preventing and treating ischemic stroke via the PI3K/Akt/eNOS and Nrf2/HO-1 pathways.

Nao-an Dropping Pill (NADP) is a Chinese patent medicine which commonly used in clinic for ischemic stroke (IS). However, the material basis and mechanism of its prevention or treatment of IS are unclear, then we carried out this study. 52 incoming blood components were resolved by UHPLC-MS/MS from rat serum, including 45 prototype components. The potential active prototype components hydroxysafflor yellow A, ginsenoside F1, quercetin, ferulic acid and caffeic acid screened by network pharmacology showed strongly binding ability with PIK3CA, AKT1, NOS3, NFE2L2 and HMOX1 by molecular docking. In vitro oxygen-glucose deprivation/reperfusion (OGD/R) experimental results showed that NADP protected HA1800 cells from OGD/R-induced apoptosis by affecting the release of LDH, production of NO, and content of SOD and MDA. Meanwhile, NADP could improve behavioral of middle cerebral artery occlusion/reperfusion (MCAO/R) rats, reduce ischemic area of cerebral cortex, decrease brain water and glutamate (Glu) content, and improve oxidative stress response. Immunohistochemical results showed that NADP significantly regulated the expression of PI3K, Akt, p-Akt, eNOS, p-eNOS, Nrf2 and HO-1 in cerebral ischemic tissues. The results suggested that NADP protects brain tissues and ameliorates oxidative stress damage to brain tissues from IS by regulating PI3K/Akt/eNOS and Nrf2/HO-1 signaling pathways.

Genome-wide DNA methylome and transcriptome profiling reveals key genes involved in the dysregulation of adipose-stem cells in Crohn's disease.

Crohn's disease (CD) is characterised by the expansion of mesenteric adipose tissue (MAT), named creeping fat (CF), which seems to be directly related to disease activity. Adipose-stem cells (ASCs) isolated from the CF of patients with CD are extremely pro-inflammatory, which persists during disease remission. We hypothesised that the dysfunctional ASCs in CD accumulate epigenetic modifications triggered by the inflammatory environment that could serve as molecular markers. Genome-wide DNA methylome and transcriptome profiling were performed in ASCs isolated from MAT adipose-tissue biopsies of patients with active and inactive disease and from non-Crohn's disease patients (non-CD). A validation cohort was used to test the main candidate genes via qPCR in other fat depots and immune cells. We found differences in DNA-methylation and gene expression between ASCs isolated from patients with CD and from non-CD subjects, but we found no differences related to disease activity. Pathway enrichment analysis revealed that oxidative stress and immune response were significantly enriched in active CD and integration analysis identified MAB21L2, a cell fate-determining gene, as the most affected gene in CD. Validation analysis confirmed the elevated gene expression of MAB21L2 in MAT and in adipose tissue macrophages in active CD. We also found a strong association between expression of the calcium channel subunit gene CACNA1H and disease remission, as CACNA1H expression was higher in ASCs and MAT from patients with inactive CD, and correlates negatively with C-reactive protein in peripheral blood mononuclear cells. We identified a potential gene signature of CD in ASCs obtained from MAT. Integration analysis highlighted two novel genes demonstrating a negative correlation between promoter DNA methylation and transcription: one linked to ASCs in CD (MAB21L2) and the other (CACNA1H) related to disease remission.

Boswellic Acid and Betulinic Acid Pre-treatments Can Prevent the Nephrotoxicity Caused by Cyclophosphamide Induction.

Cyclophosphamide (CYP) is a chemotherapeutic drug used to treat various cancers. However, its clinical use is limited due to severe organ damage, particularly to the kidneys. While several phytochemicals have been identified as potential therapeutic targets for CYP nephrotoxicity, the nephroprotective effects of boswellic acid (BOSW) and betulinic acid (BET) have not yet been investigated. Our study used 42 rats divided into six equal groups. The study included six groups: control, CYP (200 mg/kg), CYP+BOSW20 (20mg/kg), CYP+BOSW40 (40 mg/kg), CYP+BET20 (20 mg/kg), and CYP+BET40 (40 mg/kg). The pre-treatments with BOSW and BET lasted for 14 days, while the application of cyclophosphamide was performed intraperitoneally only on the 4th day of the study. After the experimental protocol, the animals were sacrificed, and their kidney tissues were isolated. Renal function parameters, histological examination, oxidative stress, and inflammation parameters were assessed both biochemically and at the molecular level in kidney tissue. The results showed that oxidative stress and inflammatory response were increased in the kidney tissue of rats treated with CYP, leading to impaired renal histology and function parameters (p < 0.05). Oral administration of both doses of BET and especially high doses of BOSW improved biochemical, oxidative, and inflammatory parameters significantly (p < 0.05). Histological studies also showed the restoration of normal kidney tissue architecture. BOSW and BET have promising biological activity against CYP-induced nephrotoxicity by attenuating inflammation and oxidative stress and enhancing antioxidant status.

Beta-Cyfluthrin-Induced Hepatic Alterations in Zebrafish: Enzymatic Profiles and Oxidative Stress Responses

Beta-Cyfluthrin is a widely used pesticide belonging to class of synthetic pyrethroids which affects the central and peripheral nervous systems. The current study investigates the impact of beta-Cyfluthrin on the biochemical parameters of liver of zebrafish (Danio sp.). Adult zebrafish were exposed to concentrations of 0.25, 0.5, 1.0, 2.0 and 4.0 µg/L of beta-Cyfluthrin for acute (96 hours) and chronic (21 days) exposure periods respectively (n=20). It was observed that exposure to beta-Cyfluthrin led to variations in biochemical markers in both acute and chronic exposure groups. Liver function tests revealed significant elevated activity of alanine transaminase (ALT) and aspartate transaminase (AST) at exposure concentrations of 2.0 and 4.0 µg/L of beta-Cyfluthrin in both acute and chronic groups, while acid phosphatase (ACP) and alkaline phosphatase (ALP) activity decreased significantly at concentrations of 1.0, 2.0 and 4.0 µg/L in the chronic group. Lipid peroxidation exhibited a concentration and time-dependent increase with significant difference at 1.0, 2.0 and 4.0 µg/L in both acute and chronic groups, while superoxide dismutase (SOD) and peroxidase (PER) levels declined significantly in both acute and chronic exposure groups at exposure concentrations of 1.0, 2.0 and 4.0 µg/L for SOD and 2.0 and 4.0 µg/L for PER. Catalase (CAT) initially increased significantly in acute groups of 1.0, 2.0 and 4.0 µg/L but decreased in chronic ones. Glutathione S-transferase (GST) levels exhibited a significant increase at lower concentrations of 0.25 µg/L but a decrease at higher concentrations, 1.0, 2.0 and 4.0 µg/L of beta-Cyfluthrin. The level of significance were considered at p&lt;0.05 and p&lt;0.01. This research suggests that exposure to beta-Cyfluthrin leads to hepatic damage in adult zebrafish. This indicates a potential risk to non-target aquatic fauna, through runoff where beta-Cyfluthrin is used as an agricultural pesticide.

Biomedical Applications of Cold Atmospheric Plasma: Cancer Therapy and Virus Inactivation

Cold atmospheric plasma (CAP), known for its ability to generate Reactive Oxygen Species (ROS) and Reactive Nitrogen Species (RNS), has emerged as a promising tool in many biomedical applications, including cancer therapeutics and virus inactivation. In cancer therapy, ROS and RNS induced by plasma have been shown to selectively target cancer cells, triggering apoptosis and inhibiting tumor growth while sparing healthy cells. This selective cytotoxicity makes plasma an attractive option for localized cancer treatment with minimal side effects. Additionally, the antimicrobial properties of ROS and RNS make plasma an effective agent for virus inactivation. By connecting the dots between cancer therapy and virus disinfection, this review paper sheds light on the potential of plasma-generated ROS and RNS as versatile tools in medical applications, offering a dual benefit of targeted cancer treatment and effective virus control. Specifically, this review explores the effects of CAP treatment on B16 melanoma cells, assessing changes in cell viability, proliferation, apoptosis and oxidative stress response. Dichloroacetate (DCA), a mitochondrial modulator, has shown promise in inducing apoptosis in melanoma cells. However, its clinical use is limited by side effects related to its neurotoxicity and suspected carcinogenicity. The potential of CAP in enhancing the therapeutic efficacy of DCA on B16-F10 melanoma apoptosis is also explored. CAP therapeutics for other types of cancers are also explored in this review. Alongside its implications in oncology, CAP has gathered substantial attention for its extraordinary potential in neutralizing viruses. CAP’s exceptional precision in targeting viral envelopes, genetic material and structural components disrupts their integrity and vital functions. This orchestrated mechanism offers a swift and efficacious route to render viruses inactive, encompassing both enveloped and nonenveloped viral types. In parallel pursuit, this review examines CAP-generated reactive species’ proficiency in deactivating SARS-CoV-2 across various surfaces. The inquiry entails subjecting surfaces to CAP treatment, succeeded by quantifying viral load and scrutinizing viral integrity. The outcomes gleaned from these investigations provide pivotal insights into CAP’s potential as a robust surface disinfection strategy, poised to combat the propagation of viral transmission.

Exploring the molecular mechanism of Epimedium for the treatment of ankylosing spondylitis based on network pharmacology, molecular docking, and molecular dynamics simulations.

Ankylosing spondylitis (AS) is a rheumatic disease that causes inflammation and bone formation in the spine. Despite significant advances in treatment, adverse side effects have triggered research into natural compounds. Epimedium (EP) is a traditional Chinese herb with a variety of pharmacological activities, including antirheumatic, anti-inflammatory, and immunomodulatory activities; however, its direct effects on AS treatment and the underlying molecular mechanisms have not been systematically studied. Thus, here, we used network pharmacology, molecular docking, and molecular dynamics simulations to explore the targets of EP for treating AS. We constructed an interaction network to elucidate the complex relationship between EP and AS. Sixteen active ingredients in EP were screened; 80 potential targets were identified. In particular, 8-(3-methylbut-2-enyl)-2-phenylchromone, anhydroicaritin, and luteolin were the core components and TNF, IL-6, IL-1β, MMP9, and PTGS2 were the core targets. The GO and KEGG analyses indicated that EP may modulate multiple biological processes and pathways, including the AGE-RAGE, TNF, NF-κB/MAPK, and TLR signaling pathways, for AS treatment. Molecular docking and molecular dynamics simulations showed good affinity between the active components and core targets of EP, with stable binding within 100 nanoseconds. In particular, 8-(3-methylbut-2-enyl)-2-phenylchromone possessed the highest free energy of binding to PTGS2 and TNF (-115.575 and - 87.676kcal/mol, respectively). Thus, EP may affect AS through multiple pathways, including the alleviation of inflammation, oxidative stress, and immune responses. In summary, we identified the active components and potential targets of EP, highlighting new strategies for the further experimental validation and exploration of lead compounds for treating AS.

Inflammatory corpuscle AIM2 facilitates macrophage foam cell formation by inhibiting cholesterol efflux protein ABCA1

The inflammatory corpuscle recombinant absents in melanoma 2 (AIM2) and cholesterol efflux protein ATP binding cassette transporter A1(ABCA1) have been reported to play opposing roles in atherosclerosis (AS) plaques. However, the relationship between AIM2 and ABCA1 remains unclear. In this study, we explored the potential connection between AIM2 and ABCA1 in the modulation of AS by bioinformatic analysis combined with in vitro experiments. The GEO database was used to obtain AS transcriptional profiling data; screen differentially expressed genes (DEGs) and construct a weighted gene co-expression network analysis (WGCNA) to obtain AS-related modules. Phorbol myristate acetate (PMA) was used to induce macrophage modelling in THP-1 cells, and ox-LDL was used to induce macrophage foam cell formation. The experiment was divided into Negative Control (NC) group, Model Control (MC) group, AIM2 overexpression + ox-LDL (OE AIM2 + ox-LDL) group, and AIM2 short hairpin RNA + ox-LDL (sh AIM2 + ox-LDL) group. The intracellular cholesterol efflux rate was detected by scintillation counting; high-performance liquid chromatography (HPLC) was used to detect intracellular cholesterol levels; apoptosis levels were detected by TUNEL kit; levels of inflammatory markers (IL-1β, IL-18, ROS, and GSH) were detected by ELISA kits; and levels of AIM2 and ABCA1 proteins were detected by Western blot. Bioinformatic analysis revealed that the turquoise module correlated most strongly with AS, and AIM2 and ABCA1 were co-expressed in the turquoise module with a trend towards negative correlation. In vitro experiments demonstrated that AIM2 inhibited macrophage cholesterol efflux, resulting in increased intracellular cholesterol levels and foam cell formation. Moreover, AIM2 had a synergistic effect with ox-LDL, exacerbating macrophage oxidative stress and inflammatory response. Silencing AIM2 ameliorated the above conditions. Furthermore, the protein expression levels of AIM2 and ABCA1 were consistent with the bioinformatic analysis, showing a negative correlation. AIM2 inhibits ABCA1 expression, causing abnormal cholesterol metabolism in macrophages and ultimately leading to foam cell formation. Inhibiting AIM2 may reverse this process. Overall, our study suggests that AIM2 is a reliable anti-inflammatory therapeutic target for AS. Inhibiting AIM2 expression may reduce foam cell formation and, consequently, inhibit the progression of AS plaques.

The cardiovascular toxicity of polystyrene microplastics in rats: based on untargeted metabolomics analysis.

Polystyrene microplastics (PS-MPs) exhibit multi-target, multi-dimensional, chronic, and low toxicity to the cardiovascular system. They enter the bloodstream through the gastrointestinal tract and respiratory system, altering blood parameters and conditions, inducing thrombotic diseases, and damaging myocardial tissue through the promotion of oxidative stress and inflammatory responses in myocardial cells. However, many of the links and mechanisms remain unclear. In this study, 48 wistar rats were randomly divided into four groups and exposed to different concentrations of PS-MPs: control group (0mg/kg/d), low dose group (0.5mg/kg/d), middle dose group (5mg/kg/d) and high dose group (50mg/kg/d), with 12 rats in each group. After 90 consecutive days of intragastric administration of PS-MPs, biochemical markers in myocardium, aorta and blood were detected, and HE staining was performed to observe the toxic effects of PS-mps on cardiovascular system. Furthermore, non-targeted metabolomics methods were used to analyze the effect of PS-MPs exposure on the metabolism of cardiovascular system in rats, and to explore its potential molecular mechanism. The results revealed no pathological changes in the heart and aorta following PS-MPs exposure. However, the myocardial enzyme levels in the high dose PS-MPs group of rats showed a significant increase. Moreover, exposure to polystyrene microplastics caused a disorder in lipid metabolism in rats, and led to an increase in indicators of inflammation and oxidative stress in myocardial and aortic tissues, but resulted in a decrease in the level of IL-6. Untargeted metabolomics results showed that metabolites with antioxidant and anti-inflammatory effects, including equol and 4-hydroxybenzoic acid, were significantly upregulated. These results suggest that long-term exposure to high concentrations of PS-MPs may lead to abnormal lipid metabolism and cardiovascular system damage. The mechanism may be related to oxidative stress and inflammatory response. Exogenous antioxidants and changes in own metabolites may have a protective effect on the injury. Therefore, understanding the toxicological mechanism of PS-MPs not only helps to elucidate its pathogenesis, but also provides new ideas for the treatment of chronic diseases.

Cornus mas L. Extract-Mediated Modulations of the Redox State Induce Cytotoxicity in Schizosaccharomyces pombe

The Cornus mas L. fruit is well known for having a high presence of bioactive substances that include phenolic compounds, anthocyanins, vitamins, flavonoids, carotenoids, and ursolic acid. The health-promoting effects of those substances are mainly associated with their antimicrobial, anti-inflammatory, and antioxidant properties. In this study, we investigated the role of Cornus mas L. fruit ethanolic extract on the cell vitality of a model eukaryotic organism, the yeast Schizosaccharomyces pombe. The effect of Cornus mas L. fruit ethanolic extract on cell viability was determined by analyses of cell growth and cell doubling time during exposure to the extract. To determine the ability of Cornus mas L. to reduce or induce oxidative stress, quantification of intracellular reactive oxygen species and malondialdehyde levels was performed. Additionally, the enzyme activity of superoxide dismutase and catalase was evaluated together with the determination of changes in the expression of genes related to oxidative stress response. The data suggest a dose-dependent cytotoxic effect of the Cornus mas L. fruit ethanol extract, as a higher concentration (2%) led to increased oxidative stress and reduced cell viability of S. pombe cells, while a lower concentration (0.5%) showed only a subtle effect on the analyzed parameters. This study provides a new perspective on the possible antimicrobial or medicinal properties of Cornus mas L. fruit ethanol extract due to its ability to induce oxidative stress in the cell.

Production and oxidative stress responses in a cage designed for creep-feeding lambs

This research aims to assess the production and oxidative stress reactions of lambs fed in a specially designed cage for creep feeding. For this purpose, the Akkaraman lambs (n = 60) were separated into four groups (15 individuals by two sexes and two groups), and all were fed the same ration. On the days that all the data was collected, the lambs were precisely 20, 34, 48, and 62 days old. The study included collecting data on body weights, body measures, and saliva samples from lambs. When the change in body weight was investigated, the results indicated that the differences between caged creep and control feeding groups (P = 0.343) and among the groupings concerning gender (P = 0.735) were insignificant. The importance levels of change differences in body measurements based on feeding methods and gender are withers height: P = 0.003, P = 0.198; body length: P < 0.001, P = 0.394; pectoral chest width: P = 0.030, P = 0.906; chest depth: P < 0.001, P = 0.741; chest circumference: P = 0.093, P = 0.529; back length: P = 0.221, P = 0.935; head length: P = 0.004, P = 0.072 and head width: P = 0.112, P = 0.617 calculated. The study's saliva samples, the effects were examined, and significant differences in Malondialdehyde (P = 0.014), superoxide dismutase (P = 0.029), catalase (P < 0.001), and glutathione s-transferase (P = 0.001) were discovered between control feeding and caged creep feeding methods. In ischemia-modified albumin (P > 0.05), the difference between the groups was insignificant. According to these findings, caged creep feeding systems are preferable for achieving faster growth rates in Akkaraman lambs; however, caged creep feeding techniques in bigger areas with longer periods are considered better for welfare conditions.

Physiological and molecular bases of the nickel toxicity responses in tomato

Nickel (Ni), a component of urease, is a micronutrient essential for plant growth and development, but excess Ni is toxic to plants. Tomato (Solanum lycopersicum L.) is one of the important vegetables worldwide. Excessive use of fertilizers and pesticides led to Ni contamination in agricultural soils, thus reducing yield and quality of tomatoes. However, the molecular regulatory mechanisms of Ni toxicity responses in tomato plants have largely not been elucidated. Here, we investigated the molecular mechanisms underlying the Ni toxicity response in tomato plants by physio-biochemical, transcriptomic and molecular regulatory network analyses. Ni toxicity repressed photosynthesis, induced the formation of brush-like lateral roots and interfered with micronutrient accumulation in tomato seedlings. Ni toxicity also induced reactive oxygen species accumulation and oxidative stress responses in plants. Furthermore, Ni toxicity reduced the phytohormone concentrations, including auxin, cytokinin and gibberellic acid, thereby retarding plant growth. Transcriptome analysis revealed that Ni toxicity altered the expression of genes involved in carbon/nitrogen metabolism pathways. Taken together, these results provide a theoretical basis for identifying key genes that could reduce excess Ni accumulation in tomato plants and are helpful for ensuring food safety and sustainable agricultural development.

Selective sweep analysis of the adaptability of the Yarkand hare (Lepus yarkandensis) to hot arid environments using SLAF‐seq

AbstractThe Yarkand hare (Lepus yarkandensis) inhabits arid desert areas and is endemic to China. It has evolved various adaptations to survive in hot arid environments, including stress responses, the ability to maintain water homeostasis and heat tolerance. Here, we performed a selective sweep analysis to identify the candidate genes for adaptation to hot arid environments in the Yarkand hare. A total of 397 237 single‐nucleotide polymorphisms were obtained from 80 Yarkand hares, which inhabit hot arid environments, and 36 Tolai hares (Lepus tolai), which inhabit environments with a mild climate, via specific‐locus amplified fragment sequencing. We identified several candidate genes that were associated with the heat stress response (HSPE1), oxidative stress response (SLC23A and GLRX2), immune response (IL1R1 and IRG1), central nervous system development (FGF13, THOC2, FMR1 and MECP2) and regulation of water homeostasis (CDK1) according to fixation index values and θπ ratios in the selective sweep analysis, and six of these genes (GLRX2, IRG1, FGF13, FMR1, MECP2 and CDK1) are newly discovered genes. To the best of our knowledge, this is the first study to identify candidate genes for adaptation to hot arid environments in the Yarkand hare. The results of this study enhance our understanding of the adaptation of the Yarkand hare to hot arid environments and will aid future studies aiming to functionally verify these candidate genes.

Dietary fatty acids modulate oxidative stress response to air pollution but not to infection.

Anthropogenic changes to the environment expose wildlife to many pollutants. Among these, tropospheric ozone is of global concern and a highly potent pro-oxidant. In addition, human activities include several other implications for wildlife, e.g., changed food availability and changed distribution of pathogens in cities. These co-occurring habitat changes may interact, thereby modulating the physiological responses and costs related to anthropogenic change. For instance, many food items associated with humans (e.g., food waste and feeders for wild birds) contain relatively more ω6-than ω3-polyunsaturated fatty acids (PUFAs). Metabolites derived from ω6-PUFAs can enhance inflammation and oxidative stress towards a stimulus, whereas the opposite response is linked to ω3-derived metabolites. Hence, we hypothesized that differential intake of ω6-and ω3-PUFAs modulates the oxidative stress state of birds and thereby affects the responses towards pro-oxidants. To test this, we manipulated dietary ω6:ω3 ratios and ozone levels in a full-factorial experiment using captive zebra finches (Taeniopygia guttata). Additionally, we simulated an infection, thereby also triggering the immune system's adaptive pro-oxidant release (i.e., oxidative burst), by injecting lipopolysaccharide. Under normal air conditions, the ω3-diet birds had a lower antioxidant ratio (GSH/GSSG ratio) compared to the ω6-diet birds. When exposed to ozone, however, the diet effect disappeared. Instead, ozone exposure overall reduced the total concentration of the key antioxidant glutathione (tGSH). Moreover, the birds on the ω6-rich diet had an overall higher antioxidant capacity (OXY) compared to birds fed a ω3-rich diet. Interestingly, only the immune challenge increased oxidative damage, suggesting the oxidative burst of the immune system overrides the other pro-oxidative processes, including diet. Taken together, our results show that ozone, dietary PUFAs, and infection all affect the redox-system, but in different ways, suggesting that the underlying responses are decoupled despite that they all increase pro-oxidant exposure or generation. Despite lack of apparent cumulative effect in the independent biomarkers, the combined single effects could together reduce overall cellular functioning and efficiency over time in wild birds exposed to pathogens, ozone, and anthropogenic food sources.

Therapeutic potential of vitamin D3 in mitigating high glucose‑induced renal damage: Mechanistic insights into oxidative stress inhibition and TXNIP/NLRP3 signaling pathway blockade.

In the development of diabetic nephropathy, pathological damage such as interstitial fibrosis and cell apoptosis often occur in renal tubules. In the present study, diabetic and control group mice were randomly treated with vitamin D3 or vehicle for 6 months. In addition, human renal tubular epithelial (HK-2) cells were cultured in high-glucose medium and treated with vitamin D3 or the oxidative inhibitor NAC. Immunohistochemistry, western blotting, quantitative PCR), and ELISA showed that vitamin D3 decreased the expression of α-smooth muscle actin and E-cadherin in renal tubular epithelial cells, improving interstitial fibrosis. It also downregulated the ratio of Bax/Bcl2 protein, alleviating apoptosis in renal tubular epithelial cells. Furthermore, vitamin D3 significantly inhibited oxidative stress response in renal tubular epithelial cells and blocked the (Thioredoxin Interacting Protein) TXNIP/NLRP3 inflammatory pathway. Therefore, vitamin D3 can protect renal tubular epithelial cells from fibrosis and apoptosis by inhibiting oxidative stress response and blocking the TXNIP/NLRP3 inflammatory pathway in diabetic nephropathy.

Overexpression of stress granule protein TZF1 enhances salt stress tolerance by targeting ACA11 mRNA for degradation in Arabidopsis.

Tandem CCCH zinc finger (TZF) proteins play diverse roles in plant growth and stress response. Although as many as 11 TZF proteins have been identified in Arabidopsis, little is known about the mechanism by which TZF proteins select and regulate the target mRNAs. Here, we report that Arabidopsis TZF1 is a bona-fide stress granule protein. Ectopic expression of TZF1 (TZF1 OE), but not an mRNA binding-defective mutant (TZF1H186Y OE), enhances salt stress tolerance in Arabidopsis. RNA-seq analyses of NaCl-treated plants revealed that the down-regulated genes in TZF1 OE plants are enriched for functions in salt and oxidative stress responses. Because many of these down-regulated mRNAs contain AU- and/or U-rich elements (AREs and/or UREs) in their 3'-UTRs, we hypothesized that TZF1-ARE/URE interaction might contribute to the observed gene expression changes. Results from RNA immunoprecipitation-quantitative PCR analysis, gel-shift, and mRNA half-life assays indicate that TZF1 binds and triggers degradation of the autoinhibited Ca2+-ATPase 11 (ACA11) mRNA, which encodes a tonoplast-localized calcium pump that extrudes calcium and dampens signal transduction pathways necessary for salt stress tolerance. Furthermore, this salt stress-tolerance phenotype was recapitulated in aca11 null mutants. Collectively, our findings demonstrate that TZF1 binds and initiates degradation of specific mRNAs to enhance salt stress tolerance.

Iron-related Genes and Proteins Involved in Iron Homeostasis in Animal Models of Allergic Asthma: A Systematic Review.

The involvement of the immune oxidative stress response in the pathophysiology and pathogenesis of allergic asthma is well documented. However, reports on the role of iron homeostasis in allergic asthma is scarce. Therefore, this study aims to identify iron-related genes and proteins in mouse models of allergic asthma. Related articles were identified from SCOPUS and Web of Science databases. The article search was limited to publications in English, within a 10-year period (2014 - 2023, up to 16 August 2023) and original/research papers. All identified articles were screened for eligibility using the inclusion and exclusion criteria. All eligible articles were quality appraised prior to data extraction. Five studies were selected for data extraction. Based on the extracted data, three themes and seven subthemes related to iron homeostasis were identified. The type of samples and analytical methods used were also identified. In conclusion, our study elucidates that iron-related proteins are regulated in animal models of allergic asthma. However, the currently available data do not allow us to conclude whether the disease model resulted in iron accumulation or depletion. Therefore, further studies with other related markers should be conducted.