Activity Of Detoxifying Enzymes Research Articles

Effects of Polystyrene Microplastic Exposure on Liver Cell Damage, Oxidative Stress, and Gene Expression in Juvenile Crucian Carp (Carassius auratus)

A considerable quantity of microplastic debris exists in the environment and the toxicity of these materials has a notable impact on aquatic ecosystems. In this paper, 50–500 µm polystyrene microplastics (exposure concentrations were 200 µg/L, 800 µg/L, and 3200 µg/L concentrations) were selected to study the effects of polystyrene microplastics (PS-MPs) on cell morphology, detoxification enzyme activity, and mRNA expression in the liver tissues of crucian carp juveniles. The results demonstrated that: (1) Different concentrations of PS-MPs cause varying degrees of pathological and oxidative damage to liver tissue cells of crucian carp. The higher the concentration of microplastics, the lower the antioxidant enzyme (CAT, GST, SOD) activity and the greater the tissue cell damage. These results demonstrate a typical dose–effect relationship. (2) Principal component analysis and Spearman’s correlation analysis demonstrated that four components, namely glutathione S-transferase (GST) and its related genes (GSTpi, GSTα), along with catalase (CAT), contributed the most to the observed outcome. These four components demonstrated a relatively high level of responsiveness to PS-MP exposure and can be employed as ecotoxicological indicators of microplastics. (3) This experiment evaluated five genes in three treatments, which found that PS-MPs had different effects on gene expression in the liver and the tested genes were involved in different response pathways associated with virulence. In this study, the toxicity of PS-MPs to crucian carp was determined at the cellular, protein, and mRNA expression levels, and combined with principal component analysis and correlation analysis to identify response sensitivity indicators that provide a scientific basis for ecological risk assessment and the safe use of microplastics.

Dichlormid protect wheat from fomesafen residual injury by increasing PPO expression and the photosynthesis characterize.

Fomesafen is a herbicide with long persistence in soil, causing damage to succeeding crops. Dichlormid is a widely used safener protecting maize from chloroacetanilide and thiocarbamate injury. We found that dichlormid treatment could restore the growth of wheat seedlings exposed to fomesafen stress. To explore its molecular mechanism, RNA-Seq was conducted to analysis transcript profiles between fomesafen and fomesafen+dichlormid treated wheat seedlings. The gene expression level was determined by qRT-PCR. Results showed that the up-regulated genes by dichlormid treatment were significantly enriched in pathways related to photosynthesis. The expression level of glutamyl-tRNA reductase (GTR), protoporphyrinogen IX oxidase (PPO, target of fomesafen), and magnesium chelatase (MAG) involved in chlorophyll biosynthesis was significantly up-regulated by dichlormid. And the expression level of genes in chlorophyll binding, energy biosynthesis, gibberellin biosynthesis and salicylic acid signal pathway was also validated to be significantly up-regulated by dichlormid. The detoxification enzyme activity of cytochrome P450 or glutathione S-transferase (GSTs), and their gene expression level was found to show no significant difference between fomesafen and fomesafen+dichlormid treatment. The antioxidant enzyme activity of peroxidase, superoxide, and the content malondialdehyde content was decreased by dichlormid, while the reduced glutathione content was increased by dichlormid significantly. The metabolism of fomesafen was further validated to be not influenced by dichlormid. These results suggested that dichlormid acted by increasing the expression of fomesafen target and photosynthesis related genes to alleviate fomesafen injury to wheat, but not accelerating fomesafen metabolism.

The effect of synergists on the inhibition of detoxification enzyme activities and acaricide sensitivity in Rhizoglyphus robini.

The saffron bulb mite, Rhizoglyphus robini Claparede (Acari: Acaridae), is the most important pest of the saffron crop in Iran. This pest attacks and feeds on saffron corms. For this reason, the corms are treated with acaricides before planting. The high activity of detoxification enzymes in arthropods may reduce their pesticide sensitivity. Diethyl maleate (DEM) is an inhibitor of glutathione S-transferases (GSTs), piperonyl butoxide (PBO) is an inhibitor of cytochrome P450 monooxygenases, and triphenyl phosphate (TPP) is an inhibitor of esterase activity. A filter paper method was used to determine the efficiency of these synergists in inhibiting the activity of detoxifying enzymes of R. robini. Adult mites were treated with these three synergists for 6, 12, 24, and 48 h, respectively. The activity of each detoxifying enzyme was measured and compared to the control treatment, and the inhibition percentage was calculated each time. The results showed that DEM reduced GST activity by 59.9% after 48 h, PBO inhibited cytochrome P450 activity by 30%, and TPP suppressed esterase activity by 38.5%. The most statistically significant inhibition occurred 24 h after pretreatment with each synergist. Bioassays with 24 h pretreatment showed that the sensitivity of R. robini to propargite increased by 1.6 times with PBO, 1.7 times with TPP, and 2.5 times with DEM. In conclusion, synergists and efficient inhibition of detoxifying enzymes can play a significant role in increasing the sensitivity of agricultural pests to pesticides and can be considered in managing pesticide resistance.

Negative cross-resistance to chlorfenapyr in pyrethroid-resistance house flies

The purpose of the research is to evaluate the susceptibility to deltamethrin and the pro-insecticide chlorfenapyr in a field population of Musca domestica L. compared to a laboratory strain Lab UF and to clarify a possible mechanism of crossresistance to chlorfenapyr.Materials and methods. The study was carried out on the adults of the laboratory strain Lab UF and the field population Nik of the housefly M. domestica collected from a livestock farm in the Tyumen region, where pyrethroid insecticides had been used for a long time. The toxicity of the pyrethroid deltamethrin (Delcid, 4%) and the pyrrole chlorfenapyr (Pyrafen EC, 360 g/l) against insects was estimated by the no-choice feeding test. Based on the dose-mortality response, lethal concentrations of insecticides were calculated by the probit analysis and the resistance ratio was determined. To clarify the possible mechanism of cross-resistance to chlorfenapyr in the Nik population of M. domestica, the activity of the main detoxification enzymes was determined depending on sex of the insects. In addition, the presence of the kdr-mutation providing resistance to pyrethroids was assessed by the Sanger sequencing.Results and discussion. The lethal concentrations of insecticides and the resistance ratios revealed the moderate resistance to deltamethrin and high susceptibility to chlorfenapyr in the field Nik population. A statistically significant increase in the activity of monooxygenases by 2.25–4.36 times, glutathione-S-transferase by 2.02–2.18 times, acetylcholinesterase by 1.45–1.46 times and alpha-naphthyl esterase by 1.41–1.46 times was noted in females and males of the Nik population compared to these parameters of the Lab UF strain. The presence of the kdr-mutation (L1014F) in houseflies of the field population was confirmed by the Sanger sequencing, while the kdr-his mutation (L1014H) was not detected. The results obtained allow us to suggest that resistance to deltamethrin and high susceptibility to chlorfenapyr in the field population of M. domestica are caused by the L1014F mutation and the increased P450 monooxygenase activity. Negative crossresistance can be used to develop insecticidal formulations that reduce the risk of rapid development of insecticidal resistance in M. domestica L.

RNA-seq analysis of LPS-induced immune priming in silkworms (Bombyx mori) and the role of cytochrome P450 detoxification system in the process

While immune priming has been identified in many invertebrates, the intricate mechanisms that drive this process in insects continue to be a subject of mystery. In this study, we exposed silkworm larvae to varying doses of lipopolysaccharide (LPS) to induce immune priming and assessed their survival upon challenge with Bacillus thuringiensis (Bt). Transcriptome analysis was performed to identify differentially expressed genes (DEGs) associated with immune priming. The role of CYP450 genes in this process was further explored using RNA interference (RNAi) to knockdown CYP9E2 and CYP6K1, followed by measurements of detoxification enzyme activities and reactive oxygen species (ROS) levels. We found that LPS exposure significantly increased silkworm survival rates upon Bt challenge, indicating the induction of immune priming. Transcriptome analysis revealed 549 DEGs, including a large number involved in detoxification, immunity, and metabolism, suggesting a complex regulatory network that encompasses immune responses and metabolic pathways. Functional enrichment and gene set enrichment analysis (GSEA) highlighted the activation of immune signaling pathways and the involvement of detoxification processes. Knockdown of CYP9E2 and CYP6K1 resulted in increased ROS levels, decreased detoxification enzyme activities, and reduced survival rates post-Bt challenge, implicating the critical role of these genes in immune priming and detoxification. Our findings demonstrate that LPS-induced immune priming in silkworms involves the upregulation of CYP450 genes, which play a critical role in detoxification and immune response modulation. The study provides insights into the molecular mechanisms of immune priming in insects and highlights the potential of CYP9E2 and CYP6K1 as targets for enhancing disease resistance and pest management in insects.

Enhancing therapeutic efficacy: In vivo mechanisms and biochemical effects of lycopene encapsulated in nanomicelles for acute inflammation and lipid metabolism

This study focuses on developing, characterizing, and evaluating lycopene nanomicelles formulations for their therapeutic potential in treating acute inflammation and obesity. Lycopene, a hydrophobic carotenoid with potent antioxidant, anti-inflammatory, and anticancer properties, faces challenges in bioavailability due to its poor solubility. To address this, the study utilized nanocarrier systems like liposomes, nanoparticles, and nanoemulsions to enhance the solubility, stability, and bioavailability of lycopene. The lycopene nanomicelles demonstrated significant anti-inflammatory and anticancer activities through multiple mechanisms. It inhibited the NF-κB pathway, reducing the expression of pro-inflammatory mediators, and modulated apoptotic pathways, leading to increased apoptosis and reduced cell proliferation in cancer cells. Furthermore, lycopene enhanced phase II detoxifying enzymes activity, interfered with gap junction communication, and potentially improved DNA repair mechanisms, contributing to its anticancer efficacy. In vivo studies revealed that lycopene nanomicelles effectively reduced leukocyte and neutrophil counts in an acute inflammation model, especially at higher doses, highlighting its potential as a nanodrug for inflammation management. However, the study found no significant alteration in triglyceride levels, indicating a need for further investigation into the effects of lycopene and its nanostructured forms on lipid metabolism. Biochemical analyses showed variations in liver enzyme levels, suggesting protective effects on the liver but also indicating potential pancreatic activity or stress and low glucose levels. These findings underscore the necessity for comprehensive safety evaluations. Overall, this research underscores the promising therapeutic applications of lycopene nanomicelles in inflammation and cancer while emphasizing the importance of addressing safety and metabolic effects for effective clinical translation.

Effects of sublethal concentration of thiamethoxam formulation on the wild stingless bee, Partamona helleri Friese (Hymenoptera: Apidae): Histopathology, oxidative stress and behavioral changes

Bees are pollinators of native and cultivated plants around the world. However, several factors are contributing to the decrease in their populations in recent years, with emphasis on the increasing use of insecticides in agriculture. Thiamethoxam is a neonicotinoid neurotoxicant, which binds to nicotinic acetylcholine receptors, causing hyperexcitation, paralysis and death of insects. Although thiamethoxam's target is the nervous system, it can affect other organs through ingestion, such as the midgut, affecting non-target insects such as bees. Partamona helleri Friese (Hymenoptera: Apidae) is a stingless bee, pollinator of several native and cultivated botanical families, and can be exposed to sublethal concentrations of thiamethoxam. This study evaluated the side effects of chronic oral exposure to thiamethoxam on the midgut, oxidative stress and behavior of P. helleri workers. The bees were exposed orally, for 7 days, to the approximate sublethal concentration of thiamethoxam found in pollen grains (0.09 ng/g). The results demonstrated changes in the midgut epithelium of workers treated with thiamethoxam, such as cytoplasmic vacuolization, cellular protrusions, increased apocrine transfer, mitochondrial damage, decreased proteins and neutral polysaccharides and the presence of cells undergoing autophagy and apoptosis. Sublethal concentration of thiamethoxam also induced oxidative stress, evidenced by changes in the activities of detoxification enzymes and antioxidant markers. Finally, thiamethoxam affects the bee's behavior, driving the distance covered and walking speed of this insect. The results indicate that the exposure of P. helleri workers to sublethal concentration of thiamethoxam have negative impacts upon midgut morphology and physiology and behavioral traits.

Impact of modified atmospheres enriched with carbon dioxide on the survival, biological, and physiological aspects of Aleuroglyphus ovatus (Troupeau, 1878)

Aleuroglyphus ovatus (Troupeau, 1878), a prevalent mite within stored products, inflicts substantial economic and health risks. The use of fumigants and grain protectants as methods of stored grain pest management had resulted in resistance and environmental concerns, necessitating alternative strategies. This study explored the toxicity of modified atmospheres composed of CO2, as an environmentally friendly, residue-free, and viable disinfestation alternative. The mortality of A. ovatus increased significantly with an increase in either CO2 concentration or exposure duration. Complete adult mortality was recorded after 72 h of treatment with 95% CO2. The calculated LT50 value was 30.52 h under 35% CO2, and it decreased to 11.78 h under 95% CO2. Additionally, CO2 exposure led to changes in the activity of antioxidant and detoxification enzymes in A. ovatus, indicating its physiological adaptation mechanisms under varying CO2 concentrations and the impact of these changes on development and reproductive capacity. Enzymatic assays revealed a concentration-dependent decrease in superoxide dismutase activity and an increase in catalase activity. The detoxification enzymes, glutathione S-transferase, and carboxylesterase demonstrated adaptive upregulation. The development of A. ovatus was delayed, and its reproductive capacity was reduced under CO2 stress. Population parameters, including the net reproductive rate (R0) and intrinsic rate of increase (rm) were all significantly reduced under CO2 stress, with 35% CO2 showing the severer impact. The study concludes that CO2 can be an effective tool for pest management in stored products, with 35% CO2 showing potential as a more economical option for A. ovatus extermination.

Chemical Composition, Larvicidal and Ovicidal Activities, and Enzyme Inhibition Capacity of Thymus serpyllum Essential Oils Against Spodoptera litura (Fabricius).

Due to their effectiveness at low doses and relative safety for non-target species, plant essential oils (EOs) are considered ideal alternatives to conventional pesticides for pest control. In this study, the chemical composition of Thymus serpyllum (T. serpyllum) EO was construed by Gas Chromatography-Mass Spectrometry (GC-MS), and its larvicidal and ovicidal activity against omnivorous pests Spodoptera litura (S. litura) was assessed. The effects of T. serpyllum EO on the activities of antioxidant detoxification enzymes were also measured. GC-MS analysis revealed that the main constituents of T. serpyllum EO were thymol (42.1%), p-cymene (22.4%), and γ-terpinene (18.6%). In the larvicidal toxicity experiment, the T. serpyllum EO demonstrated LC50 values of 0.606 and 0.664 mg/mL against the second- and third-instar larvae of S. litura, respectively, after 48 h exposure. Moreover, an EC50 value of 0.905 mg/mL was measured against S. litura eggs. In S. litura, T. serpyllum EO treatment reduced the enzymatic activity of ESTs and GST and, conversely, increased the enzymatic activity of AChE. Overall, this study demonstrated that T. serpyllum EO has the potential to be implemented as a novel eco-friendly insecticide against S. litura.

Effects of copper nanoparticles synthesized from the entomopathogen Metarhizium robertsii against the dengue vector Aedes albopictus (Skuse, 1894).

Aedes albopictus, known as the Asian tiger mosquito, is a significant vector for dengue fever, chikungunya, zika virus, yellow fever. Current control methods rely on chemical insecticides, which face challenges such as resistance, environmental harm, and impact on non-target species Eudrilus eugeniae and Artemia salina. This study evaluates the toxic effects of biogenic copper nanoparticles (CuNPs) synthesized using Metarhizium robertsii intracellular extract obtained from our previous research. The CuNPs were tested against A. albopictus and non-target species at 24 and 48 hours post-treatment. Results demonstrated that entomopathogenic fungi-derived CuNPs exhibited potent mosquitocidal activity, resulting in 97.33% mortality in larvae, 93.33% in pupae, and 74.66% in adults at 48 hours post-treatment. The CuNPs derived from M. robertsii showed lower LC50 values of 74.873 mg/L in larvae, 76.101 mg/L in pupae, and 136.645 mg/L in adults at 48 hours post-treatment. Additionally, 12 hours post-treatment, catalase (an antioxidant enzyme) activity decreased 1.5-fold in a dose-dependent manner, while glutathione S-transferase (a detoxification enzyme) activity increased 7.8-fold. CuNPs demonstrated lower toxicity to non-target species, with 24% mortality in A. salina and 24.44% mortality in E. eugeniae at 24 hours post-treatment. The LC50 values were 634.747 mg/L for A. salina and 602.494 mg/L for E. eugeniae at 24 hours post-treatment. These findings indicate that entomopathogenic fungi-derived CuNPs are a promising, target-specific candidate for controlling A. albopictus at various life stages (larvae, pupae, and adults).

Metabolic Dysfunction-Associated Steatotic Liver Disease Is Accompanied by Increased Activities of Superoxide Dismutase, Catalase, and Carbonyl Reductase 1 and Levels of miR-200b-3p in Mouse Models.

Metabolic dysfunction-associated steatotic liver disease (MASLD), one of the leading causes of chronic liver disorders, is characterized by hepatic lipid accumulation. MASLD causes alterations in the antioxidant defense system, lipid, and drug metabolism, resulting in impaired antioxidant status, hepatic metabolic processes, and clearance of therapeutic drugs, respectively. In the MASLD pathogenesis, dysregulated epigenetic mechanisms (e.g., histone modifications, DNA methylation, microRNAs) play a substantial role. In this study, the development of MASLD was investigated in mice fed a high-fat, high-fructose, and high-cholesterol (FFC) diet from 2 months of age, mice treated neonatally with monosodium glutamate (MSG) on a standard diet (STD), and mice treated with MSG on an FFC diet at 7 months of age and compared to control mice (C) on STD. Changes in liver histology, detoxification enzymes, epigenetic regulation, and genes involved in lipid metabolism were characterized and compared. The strong liver steatosis was observed in MSG STD, C FFC, and MSG FFC, with significant fibrosis in the latter one. Moreover, substantial alterations in hepatic lipid metabolism, epigenetic regulatory factors, and expressions and activities of various detoxification enzymes (namely superoxide dismutase, catalase, and carbonyl reductase 1) were observed in MASLD mice compared to control mice. miR-200b-3p, highly significantly upregulated in both FFC groups, could be considered as a potential diagnostic marker of MASLD. The MSG mice fed FFC seem to be a suitable model of MASLD characterized by both liver steatosis and fibrosis and substantial metabolic dysregulation.

Size effect of ZIF-8 based nanocarrier pesticide delivery system on targeted release and insecticidal activity.

Traditional chemical pesticides are easily lost by surface runoff and only small quantities reach the target, thus causing serious environmental pollution. In this work, dinotefuran@zeolitic imidazolate framework-8@polydopamine@zein (DNF@ZIF-8@PDA@zein), was constructed to deliver DNF with pH and enzyme double response of release, thereby achieving targeted release and efficient long-term pest control. DNF@ZIF-8@PDA@zein was synthesized with three hydrated diameters (249.73 ± 9.99 nm, 142.94 ± 5.63 nm and 75.16 ± 4.66 nm, respectively). The release of DNF from DNF@ZIF-8@PDA@zein after 28 h was significantly higher at pH 5.0 (89.22 ± 7.18%) compared to that at pH 8 (81.8 ± 6.11%). Protease-assisted release of DNF was notably higher than that without protease (pH 5: 89.22 ± 5.55% versus 27.19 ± 3.22%; pH 8: 81.8 ± 6.11% versus 25.39 ± 3.87%). The stimuli-responsive release of DNF from DNF@ZIF-8@PDA@zein increased with decreased particle size due to increased pore size, reduced binding forces (i.e., weaker π-π stacking, hydrogen bonding, and Zn-N covalent bonding), and the shortening of diffusion path, leading to faster disintegration and drug release. Additionally, the anti-photolysis ability of DNF@ZIF-8@PDA@zein was 3.2 times that of pure DNF. The insecticidal activity improved with smaller nanoparticles due to higher drug release rate and greater inhibition of detoxification enzyme activity by more zinc ion (Zn2+) dissolution. The pH and enzyme dual-responsive release as well as insecticidal activity of DNF@ZIF-8@PDA@zein increase with decreased nanoparticle size, showing effective pest management in long-term and potential application prospects in sustainable agriculture. © 2024 Society of Chemical Industry.

Transcriptional and physiological plasticity of the green peach aphid (Hemiptera: Aphididae) to cabbage and pepper plants.

Defensive metabolites and nutrient restriction of host plants are 2 major obstacles to the colonization of insect herbivores. The green peach aphid (GPA) Myzus persicae (Sulzer) broadly colonizes plants with diverse nutritional and defensive traits. However, how GPA adapts to nutritional and defensive traits within different plants remains largely unknown. To elucidate this, we first investigated the performances and transcriptomes of GPA feeding on cabbage Brassica oleracea and pepper Capsicum annuum. The green peach aphid had lower weight and fecundity when feeding on cabbage than on pepper. The transcriptomic analysis found 824 differentially expressed genes (DEGs), and 13 of the top 20 Kyoto Encyclopedia of Genes and Genomes pathways are related to nutrient metabolism, energy metabolism, and detoxification. Specifically, we found 160 DEGs associated with the metabolism of protein and amino acids, sugar and lipids, and xenobiotic substances, 86 upregulated in cabbage-fed GPA. Fourteen cathepsin B genes were strongly upregulated in cabbage-fed GPA, and were enriched in lysosome pathway and 2 dominated gene ontology terms peptidase activity and proteolysis. In addition, cabbage-fed GPA upregulated sugar and lipid digestion, while downregulated lipid biosynthesis processes. Furthermore, 55 metabolic detoxification enzyme genes were differentially expressed between GPA on 2hosts, and detoxification enzyme activities of GPA indeed changed accordingly to the host. Then, we found that cabbage has lower amino acids nutrition quality for GPA compared to pepper. Our results suggested that adjustment of nitrogen nutrient metabolism, sugar and lipid metabolism, and metabolic detoxification in a host-specific manner play crucial roles in the adaptations of GPA to different host plants.

Clinical formulation Zhigan Oral Liquid intervenes in alcoholic liver injury by regulating the intestinal flora and PI3K⧵AKT⧵NF-κB pathway

IntroductionZhigan Oral Liquid (ZOL) was developed from the empirical formulation of Professor Zhao Wenxia, a nationally renowned practitioner of Chinese medicine, and it has been used in Chinese medicine for many years for the effective treatment of alcoholic liver damage (ALD). However, the interventional mechanism of action of the dosage indications for different stages of ALD pathogenesis is not clear. MethodsThe main chemical components of ZOL were qualitatively analyzed by ultra-high performance liquid chromatography (UHPLC-Q-Orbitrap HRMS) in tandem with quadrupole electrostatic field orbital well high resolution mass spectrometry and quantitatively analyzed by high-performance liquid chromatography (HPLC). Network pharmacological analysis was performed to predict the targets and pathways of the potential pharmacodynamic components. The pharmacodynamic effects and potential target mechanisms were verified in a murine model of ALD. To observe the effect of ZOL on the intestinal flora, 16s rDNA sequencing was performed on ALD mice. ResultsZOL can achieve alcohol detoxification by increasing the activity of ALDH and other detoxification enzymes and can intervene in the process of alcoholic liver injury and liver fibrosis by regulating the alcohol-induced bacterial dysbiosis, increasing the level of antioxidants, and inhibiting the activation of the PI3K\\AKT\\NF-κB signaling pathway. Kakkalide, Luteolin, Puerarin, tectoridin, and dihydromyricetin are related to the flavonoids that may be the main pharmacodynamic components that exert their medicinal effects. ConclusionsThe findings have significant implications for the development of Empirical treatments for alcoholic liver injury. Furthermore, the study contributes to promoting development and utilization of new dosage forms of hospital preparations by emphasizing the composition identification and animal experimental efficacy of ZOL. Overall, this study provides valuable insights into establishing an alcohol-induced liver injury model, and demonstrates the potential of ZOL as a common treatment for alcoholic liver injury a rich source.

Microplastics originated from Plasmix-based materials caused biochemical and behavioral adverse effects on Daphnia magna

The implementation of advanced recycling techniques represents a key strategy for mitigating the mismanagement and the environmental impact of plastic waste. A limited array of plastic polymers can be efficiently recycled, while a notable portion of plastic waste remains unrecyclable. In Italy, this residual, heterogeneous fraction is referred to as Plasmix. Because of its complexity and non-homogeneous composition, Plasmix is primarily directed towards low-value applications. However, recent developments in laboratory-scale mechanical recycling have enabled the creation of new plastic materials from Plasmix. Prior to their application, these materials must undergo rigorous eco-safety evaluation. The present study aims to assess the potential toxicity of microplastics (MPs) from Plasmix-based materials on the freshwater crustacean Daphnia magna. Specifically, this study investigated sub-individual and individual effects induced by a 21-day exposure to different concentrations of MPs generated from the grinding of naïve and Additivated Plasmix-based materials (hereafter referred to as Px-MPs and APx-MPs, respectively). Sub-individual endpoints focused on changes in oxidative status, including the modulation of antioxidant and detoxifying enzyme activities, as well as oxidative damage, such as lipid peroxidation. Individual level endpoints included alterations in survival and reproduction. Microscopy analyses confirmed the ingestion of both Px-MPs and APx-MPs by D. magna individuals. An oxidative stress condition raised in organisms exposed to Px-MPs, whereas no effect was observed in individuals exposed to APx-MPs. Although survival was not affected, a significant impairment in reproductive output was detected at the end of exposure to all the concentrations of both MP types. These findings suggest that even low concentrations of Px-MPs and APx-MPs could negatively affect the health status of D. magna, underscoring the need for further research to complete the risk assessment of Plasmix-based materials prior to their use in consumer products.

Resveratrol and Its Natural Analogs Mitigate Immune Dysregulation and Oxidative Imbalance in the Endometriosis Niche Simulated in a Co-Culture System of Endometriotic Cells and Macrophages.

Background: Inflammation and immune cell dysfunction are critical facilitators of endometriosis pathophysiology. Macrophages are renowned for stimulating lesion growth, vascularization, innervation, and pain generation. By combining macrophages and endometriotic cells, we determined if resveratrol and its natural analogs can target the immune dysregulation and oxidative imbalance in endometriosis. Methods: After treatment with compounds (5, 10, 25 µM), we evaluated the expression of key inflammatory and oxidative stress markers, cytokines release, and ROS production by applying q-PCR, ELISA, Cytometric Beads Array, and multiplexed fluorogenic staining and flow cytometry analysis with bioimaging. Results: The results showed that endometriosis-related macrophages treated with stilbenes have impaired expression of pro-inflammatory markers (IL6, IL8, IL1B, TNF, CCL2, CXCL10, PTGS2). The effect of resveratrol, pterostilbene, and piceatannol was observed, especially in reducing IL1B, CCL2, and CXCL10 genes up to 3.5-, 5-, and 7.7-fold at 25 µM, respectively. Also, with piceatannol or polydatin exposure, the IL-6 decrease was noticeable. This study reported an antioxidant effect by reducing ROS-positive cells from 96% to 48% by pterostilbene. Results from flow cytometry correlated with the transcript activation of detoxification enzymes (SOD, GPX). Conclusions: Prospects for potential therapy based on regulating the immune microenvironment and reducing the accumulation of free radicals with stilbenes application were described in the article.

Estimating Anticancer Effects of Yohimbine in DMBA-Induced Oral Carcinogenesis Hamster Model: Utilizing Biochemical and Immunohistochemical Techniques.

Yohimbine is a potent bioactive indole alkaloid, isolated from a variety of biological sources and has long been used as a natural stimulant and aphrodisiac, particularly to treat erectile dysfunction. However, some literature also points toward its anticancer effect in different experimental models. The current study aimed to address a clinical concern on the therapeutic utilization of yohimbine as a repurposed drug. We employed 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch carcinogenesis model juxtaposed with biochemical investigation of several detoxification and antioxidant markers, such as Cyt p450, Cyt b5, thiobarbituric acid reactive substance (TBARS), glutathione (GSH), glutathione reductase (GR), glutathione S transferase (GST), DT-diaphorase, vitamin C, vitamin E, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). The immunohistochemical assessment of cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), proliferating cell nuclear antigen (PCNA), and cyclin D1 expression were also performed to observe the effect of yohimbine on these markers. The hamsters treated with DMBA presented the growth of tumors in the buccal pouches, accompanied by significant changes in the liver and buccal mucosa levels of Phase I & II detoxification enzymes and lipid peroxidation (LPO). A significant rise in the range of 2- to 3.5-fold was observed in Cyt p450, Cyt b5, and LPO in DMBA-treated animals. However, oral administration of yohimbine significantly restored the LPO, antioxidant, and detoxifying enzyme activities. Additionally, the levels of COX-2, IL-6, PCNA, and cyclin D1 were also found to be downregulated by yohimbine treatment. In conclusion, yohimbine improved the biochemical and immunohistochemical markers of DMBA-induced oral cancer and reverted to near normal values via ameliorating the underlying inflammation and oxidative stress conditions. Our study highlighted the potential of yohimbine as anticancer agent, especially against oral cancer and suggested its possible use as repurposed drug.

Behavioral, Physiological, and Molecular Mechanisms Underlying the Adaptation of Helicoverpa armigera to the Fruits of a Marginal Host: Walnut (Juglans regia).

In northwest China, changes in cultivation patterns and the scarcity of preferred hosts have forced Helicoverpa armigera to feed on the marginal host walnut (Juglans regia). However, the mechanisms allowing this adaptation remain poorly understood. Here, we investigated the behavioral, physiological, and molecular mechanisms underlying the local adaptation of this pest to walnut fruits. The green husk and shell generally contained higher levels of phytochemicals than the kernel. Bioassays revealed that the phytochemical-rich green husk and shell were less preferred, reduced larval fitness and growth, and elevated the activity of detoxification enzymes compared to the nutrient-rich kernel, which were further supported by a larger number of upregulated detoxification genes in insects fed green husks or shells based on transcriptome sequencing. Together, these data suggest that P450 genes (LOC110371778) may be crucial to H. armigera adaptation to the phytochemicals of walnuts. Our findings provide significant insight into the adaptation of H. armigera to walnut, an alternative host of lower quality. Meanwhile, our study provides a theoretical basis for managing resistance to H. armigera larvae in walnut trees and is instrumental in developing comprehensive integrated pest management strategies for this pest in walnut orchards and other agricultural systems.

Investigating the enzymatic response of Plutella xylostella L. (Lepidoptera: Plutellidae) to Metarhizium anisopliae (Metschnikoff) Sorokin (Ascomycota: Hypocreales) Infection: A Comprehensive study

The diamondback moth (DBM), Plutella xylostella, poses a significant threat to cruciferous crops due to its resistance to conventional insecticides. Entomopathogenic fungi (EPF), such as Metarhizium anisopliae offer a promising solution for the management of P. xylostella. When exposed to lethal or sub-lethal doses of microbial insecticides especially EPF, insects often mount various immune responses as a survival mechanism, including the activation of detoxification and protective enzymes. In this study, M. anisopliae (Ma1) isolated from soil resulted in 94.00 ± 0.245 percent mortality of DBM at a conidial load of 1 x 109 conidia/ml, with an LC50 value of 2.70 x 106 conidia/ml. The activity of various detoxifying and free radical scavenging enzymes was assessed in whole-body samples of P. xylostella at varying time intervals after inoculation with the entomopathogenic fungi. The results showed that the activity of the enzymes increased after 48 h of inoculation, reaching a maximum at 96 h after inoculation. After 96 h, the activity of these enzymes started to decline significantly. In conclusion, the M. anisopliae isolate Ma1 was found to be highly effective against P. xylostella. Therefore, it could be formulated using appropriate carrier material and used as a component in Integrated pest management programs. Elevated levels of detoxification and free radical scavenging enzyme expression helps in understanding the immune mechanisms in P. xylostella in response to M. anisopliae infection.

Integrated transcriptome and 1H NMR-based metabolome to explore the potential mechanism of Spodoptera litura in response to flupyrimin

Flupyrimin (FLP) is a novel class of insecticide acting on insect nicotinic acetylcholine receptor (nAChR) and shows robust insecticidal activity. However, the toxicological effects of FLP on Spodoptera litura have not been revealed. In this study, the results showed that the larval survival rate decreased significantly with increasing concentration of FLP. The hematoxylin-eosin (HE) staining showed that FLP exposure damages the structure of the larval midgut. Additionally, FLP treatments significantly increased the activities of detoxification (GST and CarE) and digestive (α-Amylase and Trypsin) enzymes and reduced lipase activity. Transcriptome sequencing identified 855, 1493 and 735 differentially expressed genes (DEGs) at 12 h, 24 h and 48 h after exposure to 3 mM FLP, respectively. Gene function enrichment analysis revealed that DEGs were mainly related to fatty acid metabolic, protein processing in the endoplasmic reticulum and drug metabolism-cytochrome P450. The DEGs associated with food digestion and detoxification was validated by reverse-transcription quantitative PCR (RT-qPCR). Furthermore, a total of fifteen energy-related metabolites were identified, among which thirteen metabolisms were significantly influenced after FLP treatment based on 1H NMR-based metabolome analysis, including tyrosine, glucose, trehalose, malate, threonine, proline, glycine, lysine, citrate, alanine, lactate, valine, and leucine. Taken together, these results provide useful information for revealing the toxicological effect of FLP against S. litura.