Oxidative Stress Response Research Articles

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

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

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

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

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

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

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

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

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

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

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

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

Curcumin in the treatment of inflammation and oxidative stress responses in traumatic brain injury: a systematic review and meta-analysis

Background and aimTraumatic brain injury (TBI), a leading cause of high morbidity and mortality, represents a significant global public health challenge. Currently, no effective treatment for TBI exists. Curcumin, an active compound extracted from the root of Curcuma longa, has demonstrated neuroprotective properties both in vitro and in vivo. Notably, it has shown potential in reducing oxidative stress and inflammation and enhancing redox balance. This paper conducts a systematic review and meta-analysis to explore curcumin’s role in TBI animal models extensively. The findings offer valuable insights for future human clinical trials evaluating curcumin as a therapeutic supplement or nutraceutical in TBI management.MethodsComprehensive literature searches were conducted across MEDLINE, Embase, Cochrane, Web of Science, and Google Scholar databases. These searches aimed to identify relevant manuscripts in all languages, utilizing the keywords “curcumin” and “traumatic brain injury.”ResultsThe final quantitative analysis included 18 eligible articles corresponding to animal studies. The analysis revealed that curcumin significantly reduced inflammatory cytokines, including IL-1β (p = 0.000), IL-6 (p = 0.002), and TNF-α (p = 0.000), across various concentrations, time points, and administration routes. Additionally, curcumin markedly enhanced the activity of oxidative stress markers such as SOD (p = 0.000), Sir2 (p = 0.000), GPx (p = 0.000), and Nrf2 (p = 0.000), while reducing MDA (p = 0.000), 4-HNE (p = 0.001), and oxyprotein levels (p = 0.024). Furthermore, curcumin improved cerebral edema (p = 0.000) and upregulated neuroprotective factors like synapsin I (p = 0.019), BDNF (p = 0.000), and CREB (p = 0.000), without reducing mNSS (p = 0.144). About autophagy and apoptosis, curcumin increased the activity of Beclin-1 (p = 0.000) and Bcl-2 (p = 0.000), while decreasing caspase-3 (p = 0.000), the apoptosis index (p = 0.000), and P62 (p = 0.002).ConclusionCurcumin supplementation positively affects traumatic brain injury (TBI) by alleviating oxidative stress and inflammatory responses and promoting neuroprotection. It holds potential as a therapeutic agent for human TBI. However, this conclusion necessitates further substantiation through high-quality literature and additional randomized controlled trials (RCTs).Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/. The registration number of PROSPERO: CRD42023452685.

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

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

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

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

Physiological and molecular bases of the nickel toxicity responses in tomato

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

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

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

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

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

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

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

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

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

Combined toxicity of polyethylene microplastics and nickel oxide nanoparticle on earthworm (Eisenia andrei): oxidative stress responses, bioavailability and joint effect.

The co-occurrence of heavy metals and microplastics (MPs) is an emerging issue that has attracted considerable attention. However, the interaction of nickel oxide nanoparticle (nano-NiO) combined with MPs in soil was poorly researched. Here, experiments were conducted to study the influence of nano-NiO (200mg/kg) and polyethylene (PE) MPs with different concentrations (0.1, 1, and 10%) and sizes (13, 50, and 500µm) on earthworms for 28days. Compared to control, the damage was induced by PE and nano-NiO, which was evaluated by biomarker Integrated Biomarker Response index: version 2 (IBRv2) based on six biomarkers including SOD, POD, CAT, MDA, AChE, Na+/K+-ATPase and cellulase. The majority of the chosen biomarkers showed significant but complicated responses with increasing contaminant concentrations after 28days of exposure. Moreover, the joint effect was assessed as antagonism by the effect addition index (EAI). Overall, this work expands our understanding of the combined toxicity of PE and nano-NiO in soil ecosystems.

Regulation of fadR on the ROS defense mechanism in Shewanalla oneidensis.

Protein FadR is known as a fatty acid metabolism global regulator that sustains cell envelope integrity by changing the profile of fatty acid. Here, we present its unique participation in the defense against reactive oxygen species (ROS) in the bacterium. FadR contributes to defending extracellular ROS by maintaining the permeability of the cell membrane. It also facilitates the ROS detoxification process by increasing the expression of ROS neutralizers (KatB, KatG, and AhpCF). FadR also represses the leakage of ROS by alleviating the respiratory action conducted by terminal cytochrome cbb3-type heme-copper oxidases (ccoNOQP). These findings suggest that FadR plays a comprehensive role in modulating the bacterial oxidative stress response, instead of merely strengthening the cellular barrier against the environment. This study sheds light on the complex mechanisms of bacterial ROS defense and offers FadR as a novel target for ROS control research.

92A Systematic Review of Proteomics in Obesity: Unpacking the Molecular Puzzle.

The present study aims to review the existing literature to identify pathophysiological proteins in obesity by conducting a systematic review of proteomics studies. Proteomics may reveal the mechanisms of obesity development and clarify the links between obesity and related diseases, improving our comprehension of obesity and its clinical implications. Most of the molecular events implicated in obesity development remain incomplete. Proteomics stands as a powerful tool for elucidating the intricate interactions among proteins in the context of obesity. This methodology has the potential to identify proteins involved in pathological processes and to evaluate changes in protein abundance during obesity development, contributing to the identification of early disease predisposition, monitoring the effectiveness of interventions and improving disease management overall. Despite many non-targeted proteomic studies exploring obesity, a comprehensive and up-to-date systematic review of the molecular events implicated in obesity development is lacking. The lack of such a review presents a significant challenge for researchers trying to interpret the existing literature. This systematic review was conducted following the PRISMA guidelines and included sixteen human proteomic studies, each of which delineated proteins exhibiting significant alterations in obesity. A total of 41 proteins were reported to be altered in obesity by at least two or more studies. These proteins were involved in metabolic pathways, oxidative stress responses, inflammatory processes, protein folding, coagulation, as well as structure/cytoskeleton. Many of the identified proteomic biomarkers of obesity have also been reported to be dysregulated in obesity-related disease. Among them, seven proteins, which belong to metabolic pathways (aldehyde dehydrogenase and apolipoprotein A1), the chaperone family (albumin, heat shock protein beta 1, protein disulfide-isomerase A3) and oxidative stress and inflammation proteins (catalase and complement C3), could potentially serve as biomarkers for the progression of obesity and the development of comorbidities, contributing to personalized medicine in the field of obesity. Our systematic review in proteomics represents a substantial step forward in unravelling the complexities of protein alterations associated with obesity. It provides valuable insights into the pathophysiological mechanisms underlying obesity, thereby opening avenues for the discovery of potential biomarkers and the development of personalized medicine in obesity.

Mechanism of action of Coptidis Rhizome in treating periodontitis based on network pharmacology and in vitro validation

ObjectiveExplore the therapeutic mechanism of Coptidis Rhizome (CR) in periodontitis using network pharmacology, and validate it through molecular docking and in vitro experiments.MethodsScreened potential active components and target genes of CR from TCMSP and Swiss databases. Identified periodontitis-related target genes using GeneCards. Found common target genes using Venny. Conducted GO and KEGG pathway analysis. Performed molecular docking and in vitro experiments using Berberine, the main active component of CR, on lymphocytes from healthy and periodontitis patients. Assessed effects on inflammatory factors using CCK-8, flow cytometry, and ELISA.ResultsFourteen active components and 291 targets of CR were identified. 30 intersecting target genes with periodontitis were found. GO and KEGG analysis revealed oxidative stress response and IL-17 signaling pathway as key mechanisms. Molecular docking showed strong binding of Berberine with ALOX5, AKT1, NOS2, and TNF. In vitro experiments have demonstrated the ability of berberine to inhibit the expression of Th17 + and other immune related cells in LPS stimulated lymphocytes, and reduce the secretion of IL-6, IL-8, and IL-17.ConclusionCR treats periodontitis through a multi-component, multi-target, and multi-pathway approach. Berberine, its key component, acts through the IL-17 signaling pathway to exert anti-inflammatory effects.

Comparative transcriptomics analysis reveals defense mechanisms of Manihot esculenta Crantz against Sri Lanka Cassava MosaicVirus

BackgroundCassava mosaic disease (CMD), caused by Sri Lankan cassava mosaic virus (SLCMV) infection, has been identified as a major pernicious disease in Manihot esculenta Crantz (cassava) plantations. It is widespread in Southeast Asia, especially in Thailand, which is one of the main cassava supplier countries. With the aim of restricting the spread of SLCMV, we explored the gene expression of a tolerant cassava cultivar vs. a susceptible cassava cultivar from the perspective of transcriptional regulation and the mechanisms underlying plant immunity and adaptation.ResultsTranscriptomic analysis of SLCMV-infected tolerant (Kasetsart 50 [KU 50]) and susceptible (Rayong 11 [R 11]) cultivars at three infection stages—that is, at 21 days post-inoculation (dpi) (early/asymptomatic), 32 dpi (middle/recovery), and 67 dpi (late infection/late recovery)—identified 55,699 expressed genes. Differentially expressed genes (DEGs) between SLCMV-infected KU 50 and R 11 cultivars at (i) 21 dpi to 32 dpi (the early to middle stage), and (ii) 32 dpi to 67 dpi (the middle stage to late stage) were then identified and validated by real-time quantitative PCR (RT-qPCR). DEGs among different infection stages represent genes that respond to and regulate the viral infection during specific stages. The transcriptomic comparison between the tolerant and susceptible cultivars highlighted the role of gene expression regulation in tolerant and susceptible phenotypes.ConclusionsThis study identified genes involved in epigenetic modification, transcription and transcription factor activities, plant defense and oxidative stress response, gene expression, hormone- and metabolite-related pathways, and translation and translational initiation activities, particularly in KU 50 which represented the tolerant cultivar in this study.

Deep Learning Bridged Bioactivity, Structure, and GC-HRMS-Readable Evidence to Decipher Nontarget Toxicants in Sediments.

Identifying causative toxicants in mixtures is critical, but this task is challenging when mixtures contain multiple chemical classes. Effect-based methods are used to complement chemical analyses to identify toxicants, yet conventional bioassays typically rely on an apical and/or single endpoint, providing limited diagnostic potential to guide chemical prioritization. We proposed an event-driven taxonomy framework for mixture risk assessment that relied on high-throughput screening bioassays and toxicant identification integrated by deep learning. In this work, the framework was evaluated using chemical mixtures in sediments eliciting aryl-hydrocarbon receptor activation and oxidative stress response. Mixture prediction using target analysis explained <10% of observed sediment bioactivity. To identify additional contaminants, two deep learning models were developed to predict fingerprints of a pool of bioactive substances (event driver fingerprint, EDFP) and convert these candidates to MS-readable information (event driver ion, EDION) for nontarget analysis. Two libraries with 121 and 118 fingerprints were established, and 247 bioactive compounds were identified at confidence level 2 or 3 in sediment extract using GC-qToF-MS. Among them, 12 toxicants were analytically confirmed using reference standards. Collectively, we present a "bioactivity-signature-toxicant" strategy to deconvolute mixtures and to connect patchy data sets and guide nontarget analysis for diverse chemicals that elicit the same bioactivity.