Glutathione S-transferase Research Articles

Insecticide resistance in the field populations of the Asian tiger mosquito Aedes albopictus in Beijing: resistance status and associated detoxification genes

BackgroundAedes (Stegomyia) albopictus (Skuse) is an invasive and widespread mosquito species that can transmit dengue, chikungunya, yellow fever, and Zika viruses. Its control heavily relies on the use of insecticides. However, the efficacy of the insecticide-based intervention is threatened by the increasing development of resistance to available insecticides. Understanding the current status and potential mechanisms of insecticide resistance is an important prerequisite for devising strategies to maintain the sustainability of vector control programs. In this study, we investigated the current status and probable candidate detoxification genes associated with insecticide resistance in the Asian tiger mosquito in Beijing, the capital city of China.MethodsBioassays were conducted on three field populations of Ae. albopictus collected from urban communities in Beijing by exposure to diagnostic doses of permethrin, deltamethrin, malathion, and propoxur. Differentially expressed genes (DEGs) associated with insecticide resistance were screened by transcriptomic analysis using Illumina RNA sequencing data (RNA-seq) from 12 independent RNA libraries constructed from female strains of the three field populations and one susceptible strain.ResultsThe bioassay results indicated that all the three field populations were resistant to propoxur (carbamate), deltamethrin, and permethrin (pyrethroids), but susceptible to malathion (organophosphate). Eighteen (18) cytochrome P450s (P450s), five (5) glutathione S-transferases (GSTs), four (4) carboxy/cholinesterases (CCEs), eight (8) UDP-glycosyltransferases (UGTs), and three (3) ATP-binding cassette transporters (ABCs) were found to be significantly overexpressed in the three field populations relative to the susceptible strain via transcriptomic analysis.ConclusionThis study demonstrates that the Ae. albopictus field populations in Beijing exhibit multiple phenotypic resistance to commonly used pyrethroids and carbamate. The identification of a number of DEGs associated with insecticide resistance indicates that the mechanisms underlying resistance in field populations are complicated, and detoxifying enzymes may play important roles. The multiple resistance status detected in the three field populations suggests that resistance management strategies such as insecticide rotation and non-chemical-based measures should be implemented in order to sustain effective control of the disease vector and vector-borne diseases.

Stranded heavy fuel oil exposure causes deformities, cardiac dysfunction, and oxidative stress in marine medaka Oryzias melastigma using an oiled-gravel-column system.

Heavy fuel oil (HFO) stranded on the coastline poses a potential threat to the health of marine fish after an oil spill. In this study, an oiled-gravel-column (OGC) system was established to investigate the toxic effects of stranded HFO on marine medaka Oryzias melastigma. HFO 380# (sulfur content 2.9%) was chosen as one type of high sulfur fuel oil for acute toxicity tests. The marine medaka larvae were exposed to the OGC system effluents with oil loading rates of 0 (control), 400, 800, 1600, and 3200µg HFO/g gravel for 144h, respectively. Results showed that a prevalence of blue sac disease signs presented teratogenic effects, including decreased circulation, ventricular stretch, cardiac hemorrhage, and pericardial edema. Moreover, the treatments (800, 1600, and 3200µg oil/g gravel) induced severe cardiotoxicity, characterized by significant bradycardia and reduced stroke volume with an overt decrease in cardiac output. Additionally, the antioxidant enzyme activities, including catalase (CAT), peroxidase (POD), and glutathione S-transferase (GST) were significantly upregulated at 800-3200µg oil/g gravel except for a marked inhibition of CAT activity at 3200µg oil/g gravel. Furthermore, significantly elevated protein carbonyl (PCO) levels were detected, suggesting that the organisms suffered severe protein oxidative damage subjected to the exposure. Overall, stranded HFO 380# exposure activated the antioxidant defense system (up-regulated POD and GST activities) of marine medaka and disrupted CAT activity, which could result in an oxidative stress state (elevated PCO levels) and might further contribute to cardiac dysfunction, deformities, and mortality.

Genome-wide phylogenetic analysis and expansion of gene families involved in detoxification in Smittia aterrima (Meigen)and Smittia pratorum (Goetghebuer) (Diptera, Chironomidae)

Smittia aterrima (Meigen, 1818) and Smittia pratorum (Goetghebuer, 1927) are important indicator insects for aquatic environments, showing extensive tolerance to the environment. However, the genome-wide phylogenetic relationships and characteristics of the detoxification mechanisms in S. aterrima and S. pratorum remain unclear. Based on the genomes of the two species obtained in our preliminary studies and nine genomes from the NCBI database, we found that chironomids diverged from other mosquitoes approximately 200 million years ago (MYA), and S. aterrima and S. pratorum diverged about 30 MYA according to phylogenetic analysis. Gene family evolution analysis showed significant expansion of 43 and 15 gene families in S. aterrima and S. pratorum, respectively, particularly those related to detoxification pathways. Positive selection analysis reveals that genes under positive selection are crucial for promoting environmental adaptation. Additionally, the detoxification-associated gene families including Cytochrome P450 (CYP), Glutathione S-transferases (GST), ATP-binding cassette (ABC), carboxylesterase (CCE), and UDP-glucuronosyltransferase (UGT) were annotated. Our analysis results show that these five detoxification gene families have significantly expanded in the chironomid genomes. This study highlights the genome evolution of chironomids and their responses to mechanisms of tolerance to environmental challenges.

QTL mapping provides new insights into emamectin benzoate resistance in salmon lice, Lepeophtheirus salmonis

BackgroundThe salmon louse (Lepeophtheirus salmonis) is a parasite of wild and farmed salmonid fish, causing huge economic damage to the commercial farming of Atlantic salmon (Salmo salar) in the northern hemisphere. The avermectin emamectin benzoate (EMB) is widely used for salmon delousing. While resistance to EMB is widespread in Atlantic populations of L. salmonis, the molecular mechanisms of resistance remain to be elucidated. The aim of the present work was to obtain insights into potential EMB resistance mechanisms by identifying genetic and transcriptomic markers associated with EMB resistance.ResultsCrosses were performed between EMB-susceptible and -resistant L. salmonis, sourced from two parental strains isolated in Scotland, producing fully pedigreed families. The EMB susceptibility of individual parasites was characterised using time-to-response bioassays. Parasites of two families were subjected to double digest restriction site-associated DNA sequencing (ddRAD-seq) for simultaneous discovery of single nucleotide polymorphisms (SNPs) and genotyping. Data analysis revealed that EMB resistance is associated with one quantitative trait locus (QTL) region on L. salmonis chromosome 5. Marker-trait association was confirmed by genotyping assays for 7 SNPs in two additional families. Furthermore, the transcriptome of male parasites of the EMB-susceptible and -resistant L. salmonis parental strains was assessed. Among eighteen sequences showing higher transcript expression in EMB-resistant as compared to drug-susceptible lice, the most strongly up-regulated gene is located in the above QTL region and shows high homology to β spectrin, a cytoskeleton protein that has roles in neuron architecture and function. Further genes differentially regulated in EMB-resistant lice include a glutathione S-transferase (GST), and genes coding for proteins with predicted roles in mitochondrial function, intracellular signalling or transcription.ConclusionsMajor determinants of EMB resistance in L. salmonis are located on Chromosome 5. Resistance can be predicted using a limited number of genetic markers. Genes transcriptionally up-regulated in EMB resistant parasites include a β spectrin, a cytoskeletal protein with still incompletely understood roles in neuron structure and function, as well as glutathione S-transferase, an enzyme with potential roles in the biochemical defence against toxicants.

Identification of crucial drought-tolerant genes of barley through comparative transcriptomic analysis and yeast-based stress assay

Drought is a persistent and serious threat to crop yield and quality. The identification and functional characterization of drought tolerance-related genes is thus vital for efforts to support the genetic improvement of drought-tolerant crops. Barley is highly adaptable and renowned for its robust stress resistance, making it an ideal subject for efforts to explore genes related to drought tolerance. In this study, two barley materials with different drought tolerance were subjected to soil drought treatment, including a variety with strong drought tolerance (Hindmarsh) and a genotype with weaker drought tolerance (XZ5). Transcriptomic sequencing data from the aboveground parts of these plants led to the identification of 1,206 differentially expressed genes associated with drought tolerance. These genes were upregulated in Hindmarsh following drought stress exposure but downregulated or unchanged in XZ5 under these same conditions, or were unchanged in Hindmarsh but downregulated in XZ5. Pathway enrichment analyses suggested that these genes are most closely associated with defense responses, signal recognition, photosynthesis, and the biosynthesis of various secondary metabolites. Using protein-protein interaction networks, the ankyrin repeat domain-containing protein 17-like isoform X2 was predicted to impact other drought tolerance-related protein targets in Hindmarsh. In MapMan metabolic pathway analyses, genes found to be associated with the maintenance of drought tolerance in Hindmarsh under adverse conditions were predicted to include genes involved in the abscisic acid, cytokinin, and gibberellin phytohormone signaling pathways, genes associated with redox homeostasis related to ascorbate and glutathione S-transferase, transporters including ABC and AAAP, transcription factors such as AP2/ERF and bHLH, the heat shock proteins HSP60 and HSP70, and the sucrose non-fermenting-1-related protein kinase. Heterologous HvSnRK2 (one of the identified genes, which encodes the sucrose non-fermenting-1-related protein kinase) gene expression in yeast conferred significant drought tolerance, highlighting the functional importance of this gene as one linked with drought tolerance. This study revealed the drought tolerance mechanism of Hindmarsh by comparing transcriptomes while also providing a set of candidate genes for genetic efforts to improve drought tolerance in this and other crop species.

DEHP impairs the oxidative stress response and disrupts trace element and mineral metabolism within the mitochondria of detoxification organs.

Di(2-ethylhexyl) phthalate (DEHP), a widely utilized plasticizer in various consumer products, is classified as an endocrine disruptor and has been implicated in numerous adverse health effects, including oxidative stress, inflammation, and metabolic disturbances. Despite the growing body of literature addressing the systemic effects of DEHP, the specific influence of DEHP-induced oxidative stress on mitochondrial function within detoxification organs, particularly the liver and kidneys, remains largely unexplored. This study evaluated the effects of DEHP exposure (0, 100, 200, and 400mg/kg/day) on mitochondrial oxidative stress, trace elements, and mineral metabolism associated with signaling pathways in the liver and kidneys of rats. Altered mitochondrial oxidative stress status was indicated by impaired glucose 6-phosphate dehydrogenase (G6PD), 6-phosphoglucerate dehydrogenase (6-PGD), glutathione reductase (GR), glutathione s-transferase (GST), and glutathione peroxidase (GPx) activities, along with significant disruptions in essential minerals and trace elements, including Na, Mg, Cu, Zn, and Fe. Key oxidative stress signaling pathways, such as NF-κB, Akt, STAT3, and CREB, glucose, and tissue homeostasis, displayed dose-dependent responses to DEHP, indicating complex regulatory mechanisms. This study represents the first comprehensive investigation into DEHP-induced mitochondrial dysfunction, highlighting its effects on oxidative stress metabolism, trace element homeostasis, and cellular signaling pathways in detoxification organs. These findings provide novel insights into the mitochondrial mechanisms underlying DEHP toxicity and underscores the need for further research into the implications of plasticizer exposure on human health.

Stable Isotope and Multiomics Reveal Uptake, Translocation, and Transformation Mechanisms of Tris(2-chloroethyl) Phosphate in Wheat (Triticum aestivum L.).

Uptake, translocation, and transformation mechanisms of tris(2-chloroethyl) phosphate (TCEP) in hydroponic wheat (Triticum aestivum L.) were systematically investigated using compound-specific stable isotope and multiomics analyses in this study. Results showed that TCEP was quickly adsorbed on root epidermis and then absorbed in roots via water and anion channels as well as an active process dependent on energy. Active process and anion channel preferentially translocated TCEP-containing light carbon isotopes and dominated the transmembrane transport of TCEP to enter vascular bundle. Transcriptomic and metabolomic analyses indicated gene-encoding ATP-binding cassette (ABC) transporters and purple acid phosphatases (PAPs) and glutathione S-transferases (GSTs) involved in TCEP transport and transformation, respectively. Molecular docking simulations showed that TCEP bound to the hydrophilic cavity of ABC transporter/PAP and hydrophobic cavity of GST, and hydrogen bonding was the important driving force. The results of this study offered insights for future effective mitigation of TCEP risk in edible plants.

Selective Lipophilization of Natural Phenolic Alcohols Induced by In Situ Choline Chloride-Based Natural Deep Eutectic Solvents.

In this scientific work, a novel and green method for selective lipophilization of EVOO's bioactive phenolic alcohols (PAs), namely, tyrosol, hydroxytyrosol, and its metabolite homovanillyl alcohol as fatty acid esters, is elucidated. The PAs have been employed as hydrogen bond donors in the formation of natural deep eutectic solvents (NADES) with choline chloride (ChCl). The fast and cheap esterification method by in situ formation of choline chloride-based deep eutectic solvents promotes the derivatization of PAs with various fatty acids as acylating agents in the absence of organic solvents and catalysts. Furthermore, given the growing interest in the application of NADES formed by bioactive molecules in the pharmacological and cosmetic fields, we analyzed the activity of antioxidant enzymes, superoxide dismutase, and glutathione S-transferase of three chemical formulations obtained after the formation of PA-oleate in the H2O2-treated HaCat human keratinocytes cell line, assessing also their toxicity via the MTT assay.

Glutathione transferase VvGSTU60 is essential for proanthocyanidin accumulation and cooperates synergistically with MATE in grapes.

Proanthocyanidin, synthesized in the endoplasmic reticulum and stored in vacuoles, is key to grape and wine quality. Glutathione S-transferase (GST) plays a crucial role in proanthocyanidin accumulation. However, little is known about the mechanisms of GSTs in the process. Here, we found that a TAU-type GST VvGSTU60 is required for proanthocyanidin accumulation in Vitis vinifera. Gene expression analysis revealed a favorable correlation between the expression pattern of VvGSTU60 and proanthocyanidin accumulation in the seed of V. vinifera. We discovered that the overexpression of VvGSTU60 in grapes resulted in a significant increase in proanthocyanidin content, whereas the opposite effect occurred when VvGSTU60 was interfered with. Biochemical analysis indicates that VvGSTU60 forms homodimers and heterodimers with VvGST1. Interestingly, we also found that VvGSTU60 interacts with VvDTX41B, a MATE transporter protein localized on the tonoplast. Heterologous expression of VvDTX41B in the Arabidopsis tt12 mutant rescues the proanthocyanidin deficiency, and interfering with VvDTX41B expression in grapes remarkably reduces the accumulation of proanthocyanidin. In addition, compared with the VvGSTU60-OE callus, the content of proanthocyanidin in VvDTX41B-RNAi + VvGSTU60-OE callus was significantly decreased but higher than that in VvDTX41B-RNAi callus. The results suggest that VvGSTU60 and VvDTX41B are coordinated in proanthocyanidin accumulation. These findings offer new insights into the accumulation mechanisms of proanthocyanidin in plants and provide the molecular basis for optimizing grape quality and wine production.

Mondia whitei fruit extract abates cadmium chloride-induced nephrotoxicity via the suppression of oxidative stress in rats

Cadmium (Cd) is an industrial heavy metal that causes toxic effects to several body organs including the kidney. Medicinal plants are used in managing various diseases caused by environmental toxicants. This study aimed to evaluate the protective ability of Mondia whitei fruit extract (MWE) against nephrotoxicity induced by CdCl₂ exposure in Wistar rats. Twenty-five male Wistar rats of 90 to 130 g body weight (b.w) were used in this study. The animals were indiscriminately assigned to five groups of five animals per group. The control group were rats in group I, whereas group II to V rats were orally administered CdCl₂ (5 mg/kg body weight (b.w)) for 5 days. Simultaneously, the rats in group III to V were co-treated with 70 mg/kg b.w of silymarin, 250 and 500 mg/kg b.w of MWE, respectively. The CdCl2 significantly (p < 0.05) increased the levels of serum renal biomarkers such as urea and creatinine, total protein and albumin. Furthermore, a substantial (p < 0.05) elevation in the nitric oxide (NO) and malondialdehyde (MDA) levels, and a concomitant (p < 0.05) reduction in the kidney activities of superoxide dismutase (SOD) and glutathione transferase (GST), and the level of reduced glutathione (GSH) were observed in the CdCl2-intoxicated rats. Alterations in the kidney's histology were also noted. Nonetheless, treatment with MWE markedly returned to normal the levels of serum kidney parameters and tissue NO and MDA. In addition, the MWE significantly (p < 0.05) elevated tissue antioxidant levels and restored the kidney histology. The result of this study suggest that MWE could potentially serve as an alternative therapy in managing CdCl2-induced nephrotoxicity.

Chromobacterium biopesticide overcomes insecticide resistance in malaria vector mosquitoes.

Vector mosquito control is an integral part of malaria control. The global emergence of insecticide resistance in malaria-transmitting Anophelines has become an impediment and has created an urgent need for novel mosquito control approaches. Here, we show that a biopesticide derived from the soil-dwelling bacterium Chromobacterium sp. Panama (Csp_P) kills insecticide-resistant Anopheles mosquitoes, regardless of their resistance mechanisms. In addition, sublethal dose of Csp_P acts as a synergist to now used chemical insecticides across multiple classes. Moreover, Csp_P reduces host-seeking behavior and malaria parasite infection in vector mosquitoes in ways that further decrease transmission. Mosquito glutathione S-transferases are essential for Csp_P's mosquito-killing mechanism. Enclosed field trials in Burkina Faso, conducted in diverse ecological settings and supported by a mathematical model, have now demonstrated its potential for malaria control in settings with widespread insecticide resistance.

DYRK2 controls GSTPI expression through ubiquitination and degradation of Twist1 to reduce chemotherapy resistance caused by EMT in breast cancer.

Breast cancer (BC) poses a significant global health challenge, with chemotherapy resistance, especially to docetaxel, remaining a major obstacle in effective treatment. The molecular mechanisms underlying this resistance are critical for developing targeted therapeutic strategies. This study aims to explore the role of dual-specificity tyrosine phosphorylation-regulated kinase 2 (DYRK2), a member of the DYRK family, in docetaxel resistance in breast cancer cells and investigate its impact on cellular responses, including drug sensitivity and migration. Additionally, potential interactions between DYRK2 and Twist1, associated with epithelial-mesenchymal transition (EMT) and drug resistance, are explored. Docetaxel-resistant breast cancer cells were induced, and the expression levels of DYRK2, Twist1, and related genes were evaluated using real-time PCR and Western blotting. Lentivirus-mediated DYRK2 overexpression was employed to assess its effect on drug sensitivity, migratory ability, and Twist1 expression. The relationship between DYRK2 and Twist1 was examined, focusing on Twist1 ubiquitination. The impact of Twist1 on chemotherapy resistance and its binding to the Glutathione S-transferase Pi 1 (GSTP1) promoter were also investigated. Docetaxel-resistant cells exhibited down-regulated DYRK2 and up-regulated Twist1 expression. DYRK2 overexpression reversed drug resistance, decreased migration, and attenuated Twist1 and GST-π expression. DYRK2 was found to suppress Twist1 expression through ubiquitination, supported by decreased Twist1 phosphorylation and increased ubiquitination after DYRK2 overexpression. Twist1 overexpression counteracted DYRK2-induced drug sensitivity enhancement, promoting GST-π expression, EMT, migration, and proliferation. Twist1 was shown to bind to the GSTP1 promoter, enhancing its transcription. In vivo experiments confirmed DYRK2's ability to suppress chemoresistance in breast cancer cells. DYRK2 plays a pivotal role in overcoming docetaxel resistance in breast cancer cells by suppressing Twist1 expression through ubiquitination, impacting downstream signaling and cellular responses. This study provides valuable insights for developing targeted therapies to improve breast cancer treatment outcomes.

SGK1-Mediated Vascular Smooth Muscle Cell Phenotypic Transformation Promotes Thoracic Aortic Dissection Progression.

The occurrence of thoracic aortic dissection (TAD) is closely related to the transformation of vascular smooth muscle cells (VSMCs) from a contractile to a synthetic phenotype. The role of SGK1 (serum- and glucocorticoid-regulated kinase 1) in VSMC phenotypic transformation and TAD occurrence is unclear. Four-week-old male Sgk1F/F (Sgk1 floxed) and Sgk1F/F;TaglnCre (smooth muscle cell-specific Sgk1 knockout) mice were administered β-aminopropionitrile monofumarate for 4 weeks to model TAD. The SGK1 inhibitor GSK650394 was administered daily via intraperitoneal injection to treat the mouse model of TAD. Immunopurification and mass spectrometry were used to identify proteins that interact with SGK1. Immunoprecipitation, immunofluorescence colocalization, and GST (glutathione S-transferase) pull-down were used to detect molecular interactions between SGK1 and SIRT6 (sirtuin 6). RNA-sequencing analysis was performed to evaluate changes in the SIRT6 transcriptome. Quantitative chromatin immunoprecipitation was used to determine the target genes regulated by SIRT6. Functional experiments were also conducted to investigate the role of SGK1-SIRT6-MMP9 (matrix metalloproteinase 9) in VSMC phenotypic transformation. The effect of SGK1 regulation on target genes was evaluated in human and mouse TAD samples. Sgk1F/F;TaglnCre or pharmacological blockade of Sgk1 inhibited the formation and rupture of β-aminopropionitrile monofumarate-induced TADs in mice and reduced the degradation of the ECM (extracellular matrix) in vessels. Mechanistically, SGK1 promoted the ubiquitination and degradation of SIRT6 by phosphorylating SIRT6 at Ser338, thereby reducing the expression of the SIRT6 protein. Furthermore, SIRT6 transcriptionally inhibits the expression of MMP9 through epigenetic modification, forming the SGK1-SIRT6-MMP9 regulatory axis, which participates in the ECM signaling pathway. Additionally, our data showed that the lack of SGK1-mediated inhibition of ECM degradation and VSMC phenotypic transformation is partially dependent on the regulatory effect of SIRT6-MMP9. These findings highlight the key role of SGK1 in the pathogenesis of TAD. A lack of SGK1 inhibits VSMC phenotypic transformation by regulating the SIRT6-MMP9 axis, providing insights into potential epigenetic strategies for TAD treatment.

Effects of surfactin stress on gene expression and pathological changes in Spodoptera litura

Spodoptera litura (S. litura) is a polyphagous pest of the family Lepidoptera, which causes damage and yields losses to many crops. The long-term use of chemical pesticides for control not only seriously threatens environmental health, but also causes S. litura to develop drug resistance. Therefore, there is an urgent need to develop environmentally safe and friendly biogenic pesticides. However, the mechanism of action of the secondary metabolite (surfactin) of Bacillus Vélezensis (B. vélezensis) on lepidopteran pests (S. litura) has not been reported yet. We found that several metabolites and genes in S. litura were affected by surfactin exposure. The expressions of the metabolites (protoporphyrinogen (PPO), gluconolactone (GDL), and L-cysteate) were significantly down-regulated while glutamate and hydroxychloroquine were significantly up-regulated. The expression levels of genes related to drug metabolism and detoxification, include the glutathione s-transferase (GST) gene family and acetaldehyde dehydrogenase (ALDH), and apoptosis-inhibiting genes (seven in absentia homolog 1(SIAH1)) were significantly decreased. In addition, pathological changes occurred in intestinal wall cells, Malpighian tubule cells, and nerve cells of S. litura under surfactin stress. Conclusively, our results suggest that surfactin induces an increase in reactive oxygen species (ROS) and damages S. litura cells. Furthermore, based on the integrated analysis of transcriptomic and metabolomic data, it is hypothesized that surfactin may also trigger neurotoxicity and cardiotoxicity in S. litura while hindering the insect’s detoxification processes. This study lays a foundation for further exploration of surfactin as a potential biopesticide.

STUDY ON THE EFFECT OF METALS CONCENTRATION ON BIOCHEMICAL PARAMETERS IN OREOCHROMIS NILOTICUS OF WARWADE RESERVOIR, DUTSE, JIGAWA STATE-NIGERIA

Warwade water Reservoir and Oreochromis niloticus’s tissues (gills and liver) were evaluated by analyzing heavy metals concentrations and their effects on the oxidative stress enzyme from January to August 2022. Both field and laboratory assessments were conducted following established scientific protocols. Monthly sampling occurred between 6:00 – 7:00 am. Four stations denoted as A, B, C, and D, were chosen based on the diversity of anthropogenic activities surrounding the reservoir. The findings showed that heavy metals concentrations in the water ranked as follows: Chromium at 1.96mg/L, followed by Lead (1.74mg/L), Nickel (1.36mg/L), and Cadmium (1.03mg/L). Heavy metals values in fish tissues exhibited a significant decrease (p<0.05) in the following order for gill tissues (Pb > Cr > Ni > Cd) and liver (Pb > Cr > Cd > Ni). The recorded vlaues exceeded the recommended limits set by WHO (2021). Enzyme activities serving as oxidative stress biomarkers demonstrated a significant reduction (P<0.05) for Superoxide dismutase (SOD), Catalase (CAT) and Glutathione Transferase (GST), with higher mean activity observed in the gills with SOD (16.57 ±0.43), CAT (23.61±2.11) and GST (84.40±1.03) compared to liver samples of GST (81.10±0.51), SOD (14.32 ±1.08) and CAT (20.51±0.17) respectively. It may be inferred that the presence of metals in Oreochromis niloticus is a consequence of the discharge of pollutants into the water body, attributable to urbanization and the discharge of agrochemicals, which adversely impacted the water quality. Consequently, it is imperative to regulate uncontrolled discharges from human activities within the reservoir to mitigate the long-term degradation...

Advances in the Degradation of Polycyclic Aromatic Hydrocarbons by Yeasts: A Review

Polycyclic aromatic hydrocarbons (PAHs) are toxic organic compounds produced during the incomplete combustion of organic materials and are commonly found in the environment due to anthropogenic activities such as industrial and vehicular emissions as well as natural sources, mainly volcanic eruptions and forest fires. PAHs are well known for their bioaccumulative capacity and environmental persistence, raising concerns due to their adverse effects on human health, including their carcinogenic potential. In recent years, bioremediation has emerged as a promising, effective, and sustainable solution for the degradation of PAHs in contaminated environments. In this context, yeasts have proven to be key microorganisms in the degradation of these compounds, owing to their ability to metabolize them through a series of enzymatic pathways. This review explores the advancements in yeast-mediated degradation of PAHs, with a particular focus on the role of enzymes such as cytochrome P450 (CYPs), epoxide hydrolases (EHs), and glutathione S-transferases (GSTs), which facilitate the breakdown of these compounds. The review also discusses the applications of genetic engineering to enhance the efficiency of yeasts in PAH degradation and the use of omics technologies to predict the catabolic potential of these organisms. Additionally, it examines studies addressing the degradation of benzo[a]pyrene (BaP) by yeasts such as Debaryomyces hansenii, and the potential future implications of omics sciences for developing new bioremediation.

Antioxidant, metabolic and digestive biomarker responses of farmed Sparus aurata supplemented with Laminaria digitata

The present study aimed to investigate the effectiveness of supplemented diets with the brown macroalga Laminaria digitata in improving the antioxidant, metabolic and digestive performance in gilthead seabream (Sparus aurata), using a multi-biomarker approach. Three experimental diets supplemented with 1.5 %, 3 % and 6 % of dried powdered L. digitata were tested against a control diet. After 30 and 60 days, S. aurata juveniles were sampled and muscle, gut and liver tissues were collected. Results showed that fish fed with 1.5 % L. digitata exhibited higher specific growth rate (SGR) after 30 days. Additionally, at this supplementation level, there was a significant reduction in antioxidant enzyme activities (catalase, CAT; glutathione S-transferase, GST; superoxide dismutase, SOD) and in lipid peroxidation (LPO) in muscle and liver tissues. In contrast, gut antioxidant enzyme activity increased with higher macroalga concentrations (3 % and 6 %). Fish fed with 6 % L. digitata revealed a significant decrease in muscle aerobic potential (citrate synthase (CS) activity) but increased anaerobic capacity (lactate dehydrogenase (LDH) activity). Moreover, the 1.5 % L. digitata supplemented diets led to a significant increase in amylase activity after 30 days. After 60 days, fed with 6 % L. digitata showed lower hepatosomatic index (HSI) compared to animals fed on control diet. Additionally, trypsin activity was higher in fish fed the supplemented diets, especially at 3 % L. digitata. Pepsin activity was significantly supressed in fish fed diets with higher macroalga concentrations (3 % and 6 %). Overall, the current findings highlight the beneficial effects with lower doses of L. digitata on farmed marine fish performance and welfare. However, additional research is needed to establish the most cost-effective seaweed supplementation dose and validate this strategy at an industrial scale.

Molecular insights into the physiological impact of low-frequency noise on sea slug Onchidium reevesii: Activation of p53 signaling and oxidative stress response

To investigate the regulatory role of tumor protein p53 of sea slug (Onchidium reevesii) under oxidative stress conditions, we examined the response mechanisms of O. reevesii to low-frequency noise pollution (1000 Hz) using molecular and cellular biology techniques. We successfully cloned the O. reevesii p53 gene (Orp53) from O. reevesii, obtaining a 3356 bp sequence containing a 2727 bp open reading frame (ORF). Phylogenetic analysis revealed that O. reevesii shares a close evolutionary relationship with other molluscs, including Bulinus truncatus and Elysia marginata. Expression analysis showed that Orp53 is expressed across various tissues, with the highest expression levels in the hepatopancreas. Using RNA interference (RNAi) to silence the Orp53 gene, we found that the mRNA expressions of Orp53 and its downstream apoptosis-related genes, including cytochrome C (Cyt_C), Caspase 9, and Caspase 3, were significantly suppressed until the third day of interference (P < 0.05). Moreover, sip53 treatment resulted in significant reductions in the mRNA expression and protein levels of all studied genes (P < 0.05) compared to the noise-exposed group. In addition, the low-frequency noise exposure decreased central nervous system (CNS) viability while increasing oxidative stress markers, including reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and glutathione S-transferase (GST). On the other hand, silencing Orp53 expression via siRNA resulted in significant reductions in CNS cell viability (P < 0.05). Our study establishes a molecular basis for evaluating the consequences of marine noise pollution, confirming that low-frequency noise activates the p53 signaling pathway, oxidative stress, and that p53 can regulate oxidative stress and apoptosis-related genes.

Therapeutic potency of kaempferol against Naja haje venom induced neurotoxicity, inflammation, biological activities, and antioxidant system damage: a pre-clinical antivenom evaluation.

Naja haje envenoming manifests organ system disorders leading to severe fatalities due to the venom's toxins. The neutralizing capacity of kaempferol has been reported against some medically significant snake venoms with exception of N. haje venom (NhV). This current study assessed the neutralizing profile of kaempferol against toxicities induced by NhV using in vitro and in vivo methods. In in vitro, NhV induced wide spectrum of toxic biological activities with substantial increase in hemorrhagic, anticoagulating, and hemolytic effects. Likewise in the in vivo study, the venom caused hematological disorders by inducing acute anemia, thrombocytopenia, and leucopenia in envenomed rats. Also, the venom caused detrimental effect on the antioxidant defense system of the brain through significant (P < 0.05) elevation of malondialdehyde (MDA), nitrite (NIT), and suppression of reduce glutathione (GSH) antioxidant, superoxide dismutase (SOD), catalase (CAT), and glutathione transferase (GST) enzymes. Additionally, the levels of neurotoxicity biomarkers, monoamine oxidase (MAO) and acetylcholinesterase (AChE), and pro-inflammatory cytokines, tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), were significantly (P < 0.0.5) enhanced by NhV in the brain of envenomed rats. Severe pathohistological effects were observed in brain tissues of the envenomed rats. However, kaempferol substantially (P < 0.05) inhibited the NhV-induced biological activities, normalized the hematological disorders, enhanced antioxidants system functions, and significantly (P < 0.05) suppressed the levels of neurotoxicity biomarkers and pro-inflammatory cytokines. Severe structural alterations observed in the brain tissues were ameliorated after kaempferol treatment. Further exploration of kaempferol could lead to the development of an alternative therapy for treatment of N. haje envenoming.

Glutathione S-transferase: A keystone in Parkinson's disease pathogenesis and therapy.

Parkinson's disease is a progressive neurodegenerative disorder that predominantly affects motor function due to the loss of dopaminergic neurons in the substantia nigra. It presents significant challenges, impacting millions worldwide with symptoms such as tremors, rigidity, bradykinesia, and postural instability, leading to decreased quality of life and increased morbidity. The pathogenesis of Parkinson's disease is multifaceted, involving complex interactions between genetic susceptibility, environmental factors, and aging, with oxidative stress playing a central role in neuronal degeneration. Glutathione S-Transferase enzymes are critical in the cellular defense mechanism against oxidative stress, catalysing the conjugation of the antioxidant glutathione to various toxic compounds, thereby facilitating their detoxification. Recent research underscores the importance of Glutathione S-Transferase in the pathophysiology of Parkinson's disease, revealing that genetic polymorphisms in Glutathione S-Transferase genes influence the risk and progression of the disease. These genetic variations can affect the enzymatic activity of Glutathione S-Transferase, thereby modulating an individual's capacity to detoxify reactive oxygen species and xenobiotics, which are implicated in Parkinson's disease neuropathological processes. Moreover, biochemical studies have elucidated the role of Glutathione S-Transferase in not only maintaining cellular redox balance but also in modulating various cellular signalling pathways, highlighting its neuroprotective potential. From a therapeutic perspective, targeting Glutathione S-Transferase pathways offers promising avenues for the development of novel treatments aimed at enhancing neuroprotection and mitigating disease progression. This review explores the evident and hypothesized roles of Glutathione S-Transferase in Parkinson's disease, providing a comprehensive overview of its importance and potential as a target for therapeutic intervention.