Crucial Antioxidant Research Articles

Hemoglobin alpha is a redox-sensitive mitochondrial-related protein in T-lymphocytes

Hemoglobin subunits, which form the well-characterized, tetrameric, oxygen-carrying protein, have recently been described to be expressed in various non-canonical cell types. However, the exact function of hemoglobin subunits within these cells remains to be fully elucidated. Herein, we report for the first time, the expression of hemoglobin alpha-a1 (Hba-a1) in T-lymphocytes and describe its role as a mitochondrial-associated antioxidant. Within naïve T-lymphocytes, Hba-a1 mRNA and HBA protein are present and highly induced by redox perturbations, particularly those arising from the mitochondria. Additionally, preliminary data using a T-lymphocyte specific Hba-a1 knock-out mouse model indicated that the loss of Hba-a1 led to an exacerbated production of mitochondrial reactive oxygen species and inflammatory cytokines after a stress challenge, further supporting the role of HBA acting to buffer the mitochondrial redox environment. Interestingly, we observed Hba-a1 expression to be significantly upregulated or downregulated depending on T-lymphocyte polarization and metabolic state, which appeared to be controlled by both transcriptional regulation and chromatin remodeling. Altogether, these data suggest Hba-a1 may function as a crucial mitochondrial-associated antioxidant and appears to possess critical and complex functions related to T-lymphocyte activation and differentiation.

Genetic variation in <i>GSTP1</i> and <i>TBXA2R</i> genes: influence of Badoush cement factory pollutant

Industrial advancements, while driving economic growth, have simultaneously intensified environmental pollution levels, posing significant health risks to populations residing near industrial hubs. The release of a complex mixture of pollutants, including heavy metals, particulate matter, and volatile organic compounds, has been linked to a range of adverse health outcomes, including respiratory diseases, cardiovascular complications, and cancer. The Badoush Cement Factor in Mosul city, Nineveh, Iraq, a major industrial facility, exemplifies this challenge, emitting substantial quantities of air pollutants capable of long-range transport. This study, therefore, investigated the potential gene-environment interactions focusing on TBXA2R and GSTP1 genes and contributing to respiratory health disparities among 64 employees of the Badoush Cement Factory compared to 10 control subjects. Specifically, the study employed the tetra-primer amplification refractory mutation system-polymerase chain (ARMS-PCR) reaction technique to analyze the role of the TBXA2R gene, known for its involvement in bronchoconstriction and susceptibility to asthma, and the GSTP1 gene, encoding a crucial antioxidant enzyme protecting lung tissue from oxidative stress. By examining these genetic markers within the context of occupational exposure at the Badoush Cement Factory, this research aimed to elucidate the intricate interplay between genetic predisposition and environmental factors in determining respiratory health outcomes. The results indicated that there was no direct correlation between exposure to pollutants and genetic variation in the TBXA2R gene. However, prolonged exposure to pollutants may increase the risk of developing respiratory diseases. No significant association was found between pollutants emitted from the cement plant and genetic variation in the GSTP1 gene.

Mechanisms and Therapeutic Potential of GPX4 in Pain Modulation.

Pain, a complex symptom encompassing both sensory and emotional dimensions, constitutes a significant global public health issue. Oxidative stress is a pivotal factor in the complex pathophysiology of pain, with glutathione peroxidase 4 (GPX4) recognized as a crucial antioxidant enzyme involved in both antioxidant defense mechanisms and ferroptosis pathways. This review systematically explores GPX4's functions across various pain models, including neuropathic, inflammatory, low back, and cancer-related pain. Specifically, the focus includes GPX4's physiological roles, antioxidant defense mechanisms, regulation of ferroptosis, involvement in signal transduction pathways, and metabolic regulation. By summarizing current research, we highlight the potential of GPX4-targeted therapies in pain management.

Prolonging the oxidative stability of walnut oil by endogenous antioxidants: Phytosterol compounding for improved antioxidant capacity

Walnut oil, loaded with unsaturated fatty acids, offers significant health advantages yet is greatly vulnerable to oxidative spoilage.The investigation explored the impact of four oil extraction techniques on the inherent antioxidants, fatty acid profiles, antioxidant efficacy, and oxidation stability index (OSI) of walnut oil. The investigation utilized variance analysis coefficients and partial least squares regression analyses were conducted. It identified β-sitosterol and stigmasterol as crucial inherent antioxidant compounds. The maximal concentrations achieved through hot pressing were 943.16 mg/kg for β-sitosterol and 121.54 mg/kg for stigmasterol. Stigmasterol contribution to the DPPH radical scavenging activity was found to be 0.8224 in PLS1 (R2>0.95). Consequently, the combined effect of these antioxidants on the OSI was tested., revealing that a 2:1 ratio of these substances, under conditions of 45 ℃ ultrasound temperature and 27 minutes ultrasound duration(p<0.05), improved the OSI from 2 to 6.42.

Sex- and dose-dependent catalase increase and its clinical impact in a benzoate dose-finding, randomized, double-blind, placebo-controlled trial for Alzheimer's disease

BackgroundSex differences in Alzheimer's disease (AD) are gaining increasing attention. Previously research has shown that sodium benzoate treatment can improve cognitive function in AD patients, particularly in the female patients; and 1000 mg/day of benzoate appears more efficacious than lower doses. Catalase is a crucial endogenous antioxidant; and deficiency of catalase is regarded to be related to the pathogenesis of AD. The current study aimed to explore the role of sex and benzoate dose in the change of catalase activity among benzoate-treated AD patients. MethodsThis secondary analysis used data from a double-blind trial, in which 149 CE patients were randomized to receive placebo or one of three benzoate doses (500, 750, or 1000 mg/day) and measured with Alzheimer's disease assessment scale-cognitive subscale. Plasma catalase was assayed before and after treatment. ResultsBenzoate treatment, particularly at 1000 mg/day, increased catalase among female patients, but not among male. The increases in the catalase activity among the benzoate-treated women were correlated with their cognitive improvements. In addition, higher baseline catalase activity was associated with more cognitive improvement after benzoate treatment among both female and male patients. ConclusionsSupporting the oxidative stress theory and sex difference in AD, the finding suggest that sex (female) and benzoate dose co-determine catalase increase in benzoate-treated AD patients and the catalase increment contributes to cognitive improvement of benzoate-treated women.Trial Registration: ClinicalTrials.gov Identifier: NCT03752463.

2-Keto-L-Gulonic Acid Enhances Cold Stress Tolerance in Arabidopsis thaliana via Augmentation of Ascorbic Acid Biosynthesis and Antioxidant Defense Systems

Cold stress severely impairs plant growth, development, and yields. L-ascorbic acid (ASA), a crucial antioxidant, is pivotal in mitigating stress-induced damage. Previous research found that 2-keto-L-gulonic acid (2KGA), a precursor of ASA in its industrial production, effectively enhances the endogenous ASA content in plants. We hypothesized that 2KGA might alleviate chilling stress and tried to verify it through a cultivation experiment of Arabidopsis thaliana. The results demonstrate that the application of 2KGA significantly increased ASA content (24.58%) and up-regulated ASA biosynthetic genes in Arabidopsis at 4 °C for 24 h. Furthermore, 2KGA alleviated the decrease in fresh weight (17.05%) and total chlorophyll content (15.85%) caused by low temperatures. The contents of proline, soluble sugar (SS), soluble protein (SP), and the activities of antioxidant enzymes including superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX) were significantly increased under the 2KGA treatment at low temperatures, while the malondialdehyde (MDA) content was reduced. Moreover, 2KGA up-regulated the ICE-CBF-COR signaling pathway in response to cold stress. These collective findings strongly support the involvement of 2KGA in enhancing cold tolerance in Arabidopsis, presenting an innovative approach for agricultural practices aimed at enhancing crop resilience to environmental stresses.

Hemoglobin alpha is a redox-sensitive mitochondrial-related protein in T-lymphocytes.

Hemoglobin subunits, which form the well-characterized, tetrameric, oxygen-carrying protein, have recently been described to be expressed in various non-canonical cell types. However, the exact function of hemoglobin subunits within these cells remains to be fully elucidated. Herein, we report for the first time, the expression of hemoglobin alpha-a1 (Hba-a1) in T-lymphocytes and describe its role as a mitochondrial-associated antioxidant. Within naïve T-lymphocytes, Hba-a1 mRNA and HBA protein are present and highly induced by redox perturbations, particularly those arising from the mitochondria. Additionally, preliminary data using a T-lymphocyte specific Hba-a1 knock-out mouse model indicated that the loss of Hba-a1 led to an exacerbated production of mitochondrial reactive oxygen species and inflammatory cytokines after a stress challenge, further supporting the role of HBA acting to buffer the mitochondrial redox environment. Interestingly, we observed Hba-a1 expression to be significantly upregulated or downregulated depending on T-lymphocyte polarization and metabolic state, which appeared to be controlled by both transcriptional regulation and chromatin remodeling. Altogether, these data suggest Hba-a1 may function as a crucial mitochondrial-associated antioxidant and appears to possess critical and complex functions related to T-lymphocyte activation and differentiation.

The Protective Role of L-Cysteine in the Regulation of Blood-Testis Barrier Functions-A Brief Review.

Blood-testis barrier (BTB) genes are crucial for the cellular mechanisms of spermatogenesis as they protect against detrimental cytotoxic agents, chemicals, and pathogens, thereby maintaining a sterile environment necessary for sperm development. BTB proteins predominantly consist of extensive tight and gap junctions formed between Sertoli cells. These junctions form a crucial immunological barrier restricting the intercellular movement of substances and molecules within the adluminal compartment. Epithelial tight junctions are complex membrane structures composed of various integral membrane proteins, including claudins, zonula occludens-1, and occludin. Inter-testicular cell junction proteins undergo a constant process of degradation and renewal. In addition, the downregulation of genes crucial to the development and preservation of cell junctions could disrupt the functionality of the BTB, potentially leading to male infertility. Oxidative stress and inflammation may contribute to disrupted spermatogenesis, resulting in male infertility. L-cysteine is a precursor to glutathione, a crucial antioxidant that helps mitigate damage and inflammation resulting from oxidative stress. Preclinical research indicates that L-cysteine may offer protective benefits against testicular injury and promote the expression of BTB genes. This review emphasizes various BTB genes essential for preserving its structural integrity and facilitating spermatogenesis and male fertility. Furthermore, it consolidates various research findings suggesting that L-cysteine may promote the expression of BTB-associated genes, thereby aiding in the maintenance of testicular functions.

Influence of smoking status on the relationship between serum selenium and cause-specific mortality in US adults

Selenium, a crucial antioxidant in the body, has been linked to all-cause and cause-specific mortality. However, the relationship between selenium and mortality in the general population remains unclear. A total of 5449 participants in the National Health and Nutrition Examination Survey (NHANES) (2003–2004, 2011–2016) were analyzed to track participant mortality until December 31, 2019. The COX proportional hazard model, Kaplan‒Meier survival analysis and restricted cubic spline regression analysis were used to investigate the associations. Subgroup analysis was conducted on the basis of age (≤ 60, > 60), sex (male, female), and smoking status (nonsmoker, former smoker, and current smoker). The second quartile was associated with lower all-cause mortality and noncardiovascular mortality (HR and 95% CI 0.61,0.45–0.83;0.59,0.42–0.83, respectively). The third quartile was associated with lower cardiovascular-related mortality (HR and 95% CI 0.49, 0.32–0.76). Elevated serum selenium concentrations were associated with lower all-cause mortality, noncardiovascular mortality (range ≤ 129.82 μg/L), and cardiovascular mortality (range ≤ 129.08 μg/L). Subgroup analysis revealed a positive correlation between the serum selenium concentration (range ≥ 129.82 μg/L) and all-cause mortality among the subgroup of current smokers (p < 0.001). This study indicates that the protective effect of the serum selenium concentration on cause-specific mortality decreases beyond a certain range in the general population, potentially increasing the risk of death among current smokers.

Changes of oxidative stress in 3D film to be prepared for echocardiography: A randomized controlled study.

Echocardiography (ECHO) is a nonprocedure that causes acute stress in children. Fear, anxiety, and fluctuations in children's blood pressure and heart rate can potentially lead to alterations in echocardiographic measurements. The insufficient research on virtual reality pediatric preparation applications, particularly in the context of echocardiographic procedures, underscores the necessity for additional studies focusing on pediatric patients. This study sought to assess the impact of virtual reality applications tailored explicitly for ECHO on children's oxidative stress levels. This was a prospective, randomized, controlled experimental study. Forty-eight children (experimental/24, control/24) aged 7 to 12 years who had an ECHO appointment in the pediatric cardiology outpatient clinic in the 3 months from June to August 2019 participated in the study. Participants whose blood analyses showed hemolysis were eliminated, and the study was completed with 37 children in total: 16 children in the experiment and 21 children in the control. Post hoc power analysis was performed for sample adequacy, and the power of the study was found to be 0.99. A 3D film was prepared for the research and applied to the experimental group before the procedure. All children's oxidative stress levels (cortisol, malondialdehyde, nitric oxide) and glutathione levels were checked after ECHO. The stress hormone cortisol and malondialdehyde levels were lower in the 3D-applied experimental group than in the control group. As another crucial anti-stress antioxidant factor, glutathione level increased in the experimental group compared to the control group (P < .05). The research revealed that the 3D film used to prepare ECHO reduces the stress parameters associated with heart risk and may affect the ECHO measurements. At the same time, the study also proved the positive effect of 3D film preparation by increasing the anti-stress factor.

Association of serum uric acid levels with risk of epilepsy: A national population-based study

BackgroundUric acid (UA) serves as a crucial endogenous antioxidant in the body, offering protection against oxidative stress, whichmaycontributetoepilepsypathogenesis. The association between serum UA levels and epilepsy remains uncertain. This study aimed to examine the potential connections between serum UA levels and epilepsy in US adults. MethodsUtilizing data from the National Health and Nutrition Examination Survey (NHANES) 2013–2018, a cross-sectional analysis was conducted. Weighted logistic regression analyses were employed to assess the potential link between serum UA levels and the risk of epilepsy. Additionally, sensitivity analyses were conducted to evaluate the reliability of the results. ResultsWe included 15,373 participants, of whom 136 (0.79 %) had epilepsy. Following adjustment for multiple variables, participants with serum UA levels <4.1 mg/dl had an odds ratio of 2.24 (95 % CI: 1.12–4.47, P = 0.023) for epilepsy compared to those with serum UA levels of 5.8–6.5 mg/dl. The results of the sensitivity analyses corroborated the initial findings. ConclusionsOur study revealed a significant association between lower serum UA levels and heightened risks of epilepsy, suggesting that low UA levels may serve as an independent risk factor for epilepsy. A marginal increase in UA levels within the normal range may act as a protective factor against epilepsy.

Quantification of Glutathione and Its Associated Spontaneous Neuronal Activity in Major Depressive Disorder and Obsessive-Compulsive Disorder

BackgroundGlutathione (GSH) is a crucial antioxidant in the human brain. Although proton magnetic resonance spectroscopy using the Mescher-Garwood point-resolved spectroscopy sequence is highly recommended, limited literature has measured cortical GSH using this method in major psychiatric disorders. MethodsBy combining magnetic resonance spectroscopy and resting-state functional magnetic resonance imaging, we quantified brain GSH and glutamate in the medial prefrontal cortex and precuneus and explored relationships between GSH levels and intrinsic neuronal activity as well as clinical symptoms among healthy control (HC) participants (n = 30), people with major depressive disorder (MDD) (n = 28), and people with obsessive-compulsive disorder (OCD) (n = 28). ResultsGSH concentrations were lower in the medial prefrontal cortex and precuneus in both the MDD and OCD groups than in the HC group. In the HC group, positive correlations were noted between GSH and glutamate levels and between GSH and fractional amplitude of low-frequency fluctuations in both regions. However, while these correlations were absent in both patient groups, there was a weak positive correlation between glutamate and fractional amplitude of low-frequency fluctuations. Moreover, GSH levels were negatively correlated with depressive and compulsive symptoms in MDD and OCD, respectively. ConclusionsThese findings suggest that reduced GSH levels and an imbalance between GSH and glutamate could increase oxidative stress and alter neurotransmitter signaling, thereby leading to disruptions in GSH-related neurochemical-neuronal coupling and psychopathologies across MDD and OCD. Understanding these mechanisms could provide valuable insights into the processes that underlie these disorders and potentially become a springboard for future directions and advancing our knowledge of their neurobiological foundations.

Nano-Selenium and Glutathione Enhance Cucumber Resistance to Botrytis cinerea by Promoting Jasmonic Acid-Mediated Cucurbitacin Biosynthesis.

Nano-selenium (Nano-Se), as a biological stimulant, promotes plant growth and development, as well as defense against biotic and abiotic stresses. Glutathione (GSH) is a crucial antioxidant and is also involved in the plant defense response to various stresses. In this study, the efficacy of combined treatment of Nano-Se and GSH (SeG) on the resistance of cucumber plants to Botrytis cinerea was investigated in terms of the plant phenotype, gene expression, and levels of accumulated metabolites using transcriptomic and metabolomic analyses. The exogenous application of SeG significantly enhanced plant growth and increased photosynthetic pigment contents and capacity. Notably, B. cinerea infection was reduced markedly by 41.9% after SeG treatment. At the molecular level, the SeG treatment activated the alpha-linolenic acid metabolic pathway and upregulated the expression of genes responsible for jasmonic acid (JA) synthesis, including LOX (210%), LOX4 (430%), AOS1 (100%), and AOC2 (120%), therefore promoting JA accumulation in cucumber. Intriguingly, the level of cucurbitacin, an important phytoalexin in cucurbitaceous plants, was found to be increased in SeG-treated cucumber plants, as was the expression of cucurbitacin biosynthesis-related genes OSC (107.5%), P450 (440.8%,31.6%), and ACT (414.0%). These genes were also upregulated by JA treatment, suggesting that JA may be an upstream regulator of cucurbitacin biosynthesis. Taken together, this study demonstrated that pretreatment of cucumber plants with SeG could activate the JA signaling pathway and promote cucurbitacin biosynthesis to enhance the resistance of the plants to B. cinerea infection. The findings also indicate that SeG is a promising biostimulant for protecting cucumber plants from B. cinerea infection without growth loss.

Vanadium toxicity was alleviated by supplementation of silicon in tomato seedlings: Upregulating antioxidative enzymes and glyoxalase system

The primary goal of this research is to investigate the mitigating effect of silicon (Si; 2 mM) on the growth of tomato seedlings under vanadium (V; 40 mg) stress. V stress caused higher V uptake in leaf, and enhanced concentration of leaf anthocyanin, H2O2, O2•−, and MDA, but a decreased in plant biomass, root architecture system, leaf pigments content, mineral elements, and Fv/Fm (PSII maximum efficiency). Si application increased the concentrations of crucial antioxidant molecules such as AsA and GSH, as well as the action of key antioxidant enzymes comprising APX, GR, DHAR, and MDHAR. Importantly, oxidative damage was remarkably alleviated by upregulation of these antioxidant enzymes genes. Moreover, Si application enhanced the accumulation of secondary metabolites as well as the expression their related-genes, and these secondary metabolites may restricted the excessive accumulation of H2O2. In addition, Si rescued tomato plants against the damaging effects of MG by boosting the Gly enzymes activity. The results confirmed that spraying Si to plants might diminish the V accessibility to plants, along with promotion of V stress resistance.

Melatonin regulates the antioxidant capacity of sheep granulosa cells through a novel uORF-Nrf2aa mediated Nrf2/KEAP1 pathway

Ovarian dysfunction stands as a prevalent contributor to female infertility, with its etiology intertwined with genetic, autoimmune, and environmental factors. Within the ovarian follicles, granulosa cells (GCs) represent the predominant cell population. Alterations in GCs, notably oxidative stress (OS) and the consequential surge in reactive oxygen species (ROS), play pivotal roles in the orchestration of ovarian function. Nrf2aa, a newly identified upstream open reading frame (uORF), is situated within the 5′ untranslated region (5'UTR) of sheep Nrf2 mRNA and is regulated by melatonin, a crucial intrafollicular antioxidant. In this study, we have noted that Nrf2aa has the capacity to encode a peptide and exerts a negative regulatory effect on the translation efficiency (TE) of the Nrf2 CDs region. Further in vitro experiments, we observed that interfering with Nrf2aa can enhance the cellular functionality of GCs under 3-np-induced oxidative stress, while overexpressing Nrf2aa has the opposite effect. Furthermore, overexpression of Nrf2aa counteracts the rescuing effect of melatonin on the cellular functions of GCs under oxidative stress conditions, including estrogen secretion, proliferation, apoptosis, and many more. Finally, we confirmed that Nrf2aa, by regulating the expression of key proteins in the Nrf2/KEAP1 signaling pathway, further modulates the antioxidant levels in GCs.

Cobalt protoporphyrin modulates antioxidant enzyme activity in the hypothalamus and motor cortex of female rats.

Cobalt protoporphyrin (CoPP) is a synthetic heme analog that has been observed to reduce food intake and promote sustained weight loss. While the precise mechanisms responsible for these effects remain elusive, earlier research has hinted at the potential involvement of nitric oxide synthase in the hypothalamus. This study aimed to delve into CoPP's impact on the activities of crucial antioxidant enzymes: superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione-S-transferase (GST) across seven distinct brain regions (hippocampus, hypothalamus, prefrontal cortex, motor cortex, striatum, midbrain, and cerebellum), as well as in the liver and kidneys. Female Wistar rats weighing 180 to 200 grams received a single subcutaneous dose of 25 μmol/kg CoPP. After six days, brain tissue was extracted to assess the activities of antioxidant enzymes and quantify malondialdehyde levels. Our findings confirm that CoPP administration triggers the characteristic effects of decreased food intake and reduced body weight. Moreover, it led to an increase in SOD activity in the hypothalamus, a pivotal brain region associated with food intake regulation. Notably, CoPP-treated rats exhibited elevated enzymatic activity of catalase, GR, and GST in the motor cortex without concurrent signs of heightened oxidative stress. These results underscore a strong connection between the antioxidant system and food intake regulation. They also emphasize the need for further investigation into the roles of antioxidant enzymes in modulating food intake and the ensuing weight loss, using CoPP as a valuable research tool.

The Important Role of GPX1 and NF-κB Signaling Pathway in Human Gastric Cancer: Implications for Cell Proliferation and Invasion.

Glutathione peroxidases (GPXs) are crucial antioxidant enzymes, counteracting reactive oxygen species (ROS). GPX overexpression promotes proliferation and invasion in cancer cells. Glutathione peroxidase-1 (GPX1), the most abundant isoform, contributes to invasion, migration, cisplatin resistance, and proliferation in various cancers. Nuclear factor-kappa B (NF-[Formula: see text]B) participates in cell proliferation, apoptosis, and tumor progression. The inhibition of NF-[Formula: see text]B expression reduces the malignancy of esophageal squamous cell carcinoma. This study aimed to explore the GPX1 and NF-[Formula: see text]B signaling pathways and their correlation with gastric cancer cell proliferation and invasion. Cell culture, complementary DNA microarray analysis, western blotting, reverse transcription-polymerase chain reaction, zymography, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, GPX1 knock-down with short hairpin RNA (shRNA), standard two-chamber invasion assay, chromatin immunoprecipitation assay. Hepatocyte growth factor (HGF) up-regulated GPX1 expression in gastric cancer cells. The NF-[Formula: see text]B inhibitor, pyrrolidine dithiocarbamate down-regulated HGF-induced GPX1 protein levels. Furthermore, NF-[Formula: see text]B and urokinase-type plasminogen activators were down-regulated in GPX1-shRNA-treated cells. Treatment with an Akt pathway inhibitor (LY294002) led to the down-regulation of GPX1 and NF-[Formula: see text]B gastric cancer cells. GPX1 knockdown resulted in decreased HGF-mediated in vitro cell proliferation and invasion. The study identified the putative binding site of the GPX1 promoter containing the NF-[Formula: see text]B binding site, confirmed through chromatin immunoprecipitation. HGF induced GPX1 expression through the NF-[Formula: see text]B and Akt pathways, suggesting a central role in gastric cell proliferation and invasion. Hence, GPX1 emerges as a potential therapeutic target for gastric cancer.

Evaluating Pseudomonas monteilii JK-1 as an in-feed probiotic: Enhancing growth, immune-antioxidant, disease resistance and modulating gut microflora composition in grass carp (Ctenopharyngodon idella)

Host-derived probiotics are microorganisms sourced from the host's gut environment, aimed at enhancing growth and overall health. Given the increasing stringency in the regulation of antibiotics within animal production, the adoption of in-feed probiotics has emerged as a compelling antibiotic alternative in aquaculture. Here, we investigate the impact of Pseudomonas monteilii JK-1 on the growth performance and disease resistance of grass carp (Ctenopharyngodon idella). The results indicate that P. monteilii JK-1 leads to a significant increase in weight gain (WG), specific growth rate (SGR), and survival rate, along with a substantial reduction in pathogen load (Aeromonas) (P < 0.05). Furthermore, we observed a noteworthy improvement in the expression of key immune-related genes, including interleukin 1β (IL-1β), interleukin 10 (IL10), tumor necrosis factor alpha (TNF-α), and transforming growth factor beta (TGF-β) in both the head kidney and gut (P < 0.05). This effect extends to the augmentation of the activities of crucial antioxidant enzymes, such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) in both liver and gut tissues (P < 0.05). Notably, P. monteilii JK-1 exerts a positive influence on the complexity of the gut microbiome ecological network. In this context, Cetobacterium emerges as a keystone microbiota responsible for maintaining interspecies interactions and enhancing gut network stability. Moreover, our study establishes a positive connection between Cetobacterium and growth performance and between Akkemansia and immune response, respectively. In addition, the result of partial least squares path model (PLS-PM) showed that P. monteilii JK-1 does not directly enhance growth performance and pathogen resistance but does so by regulating keystone taxa and promoting gut network stability. Collectively, this study offers a nuanced comprehension of how probiotics enhance growth and boost disease resistance, focusing on the gut microbial ecological network. These findings showed that P. monteilii JK-1 has potential application as a probiotic in grass carp, which may provide a new strategy of preventing and controlling bacterial diseases in this species.

Isoenzyme characterization of Leishmania infantum toward checking the antioxidant activity of superoxide dismutase and glutathione peroxidase

BackgroundLeishmania infantum is the major causative agent of visceral leishmaniasis in Mediterranean regions. Isoenzyme electrophoresis (IE), as a biochemical technique, is applied in the characterization of Leishmania species. The current study attempted to investigate the isoenzyme patterns of logarithmic and stationary promastigotes and axenic amastigotes (amastigote-like) of L. infantum using IE. The antioxidant activity of superoxide dismutase (SOD) and glutathione peroxidase (GPX) was also checked in the aforementioned forms.MethodAfter L. infantum cultivation and obtaining logarithmic and stationary promastigotes, axenic amastigotes were achieved by incubation of stationary promastigotes at 37 °C for 48 h. The lysate samples were prepared and examined for six enzymatic systems including glucose-6-phosphate dehydrogenase (G6PD), nucleoside hydrolase 1 (NH1), malate dehydrogenase (MDH), glucose-phosphate isomerase (GPI), malic enzyme (ME), and phosphoglucomutase (PGM). Additionally, the antioxidant activity of SOD and GPX was measured.ResultsGPI, MDH, NH1, and G6PD enzymatic systems represented different patterns in logarithmic and stationary promastigotes and axenic amastigotes of L. infantum. PGM and ME showed similar patterns in the aforementioned forms of parasite. The highest level of SOD activity was determined in the axenic amastigote form and GPX activity was not detected in different forms of L. infantum.ConclusionThe characterization of leishmanial-isoenzyme patterns and the measurement of antioxidant activity of crucial antioxidant enzymes, including SOD and GPX, might reveal more information in the biology, pathogenicity, and metabolic pathways of Leishmania parasites and consequently drive to designing novel therapeutic strategies in leishmaniasis treatment.

Hspb1 protects against severe acute pancreatitis by attenuating apoptosis and ferroptosis via interacting with Anxa2 to restore the antioxidative activity of Prdx1.

Acute pancreatitis (AP) is a common abdominal disease that typically resolves on its own, but the mortality rate dramatically increases when it progresses to severe acute pancreatitis (SAP). In this study, we investigated the molecular mechanism underlying the development of SAP from AP. We utilized two SAP models induced by pancreatic duct ligation and caerulein administration. Transcriptomic and proteomic analyses were subsequently performed to determine the mRNA and protein expression profiles of pancreatic samples from SAP and AP model and normal mice. To explore the role of Hspb1 in SAP, we used Hspb1 knockout (KO) mice, a genetically engineered chronic pancreatitis strain (T7D23A), Anxa2 KO mice, and acinar cell-specific Prdx1 knockout mice. Additionally, various in vivo and in vitro assays were performed to elucidate the molecular events and direct targets of Hspb1 in acinar cells. We found that Hspb1 expression was upregulated in AP samples but significantly reduced in acinar cells from SAP samples. KO or inhibition of Hspb1 worsened AP, while AAV8-Hspb1 administration mitigated the severity of SAP and reduced remote organ damage in mice. Furthermore, AAV8-Hspb1 treatment prevented the development of chronic pancreatitis. We found that KO or inhibition of Hspb1 promoted acinar cell death through apoptosis and ferroptosis but not necroptosis or autophagy by increasing reactive oxygen species (ROS) and lipid ROS levels. Mechanistically, Hspb1 directly interacted with Anxa2 to decrease its aggregation and phosphorylation, interact with the crucial antioxidant enzyme Prdx1, and maintain its antioxidative activity by decreasing Thr-90 phosphorylation. Notably, the overexpression of Hspb1 did not have a protective effect on acinar-specific Prdx1 knockout mice. In summary, our findings shed light on the role of Hspb1 in acinar cells. We showed that targeting Hspb1/Anxa2/Prdx1 could serve as a potential therapeutic strategy for SAP.