Oxidative Stress-related Genes Research Articles

Water Versus Electrolyte Rehydration on Vocal Fold Osmotic and Oxidative Stress Gene Expression.

Systemic dehydration may induce osmotic and oxidative stress in the vocal folds, but our knowledge of the biology and mitigation with rehydration is limited. The purpose of this experiment was to evaluate whether systemic dehydration induces vocal fold oxidative and osmotic stress and to compare the impact of rehydration by water intake versus electrolyte intake on osmotic and oxidative stress-related gene expression. Four-month-old male Sprague-Dawley rats (N = 32) underwent water restriction. Rehydration was achieved with ad libitum access to water or electrolytes for 24 hours. Rats were divided into four groups: euhydration control, dehydration-only, dehydration followed by either water or electrolyte rehydration (n = 8/group). Gene expression was assessed via RT2 Gene Expression Profiler arrays. With respect to oxidative stress, 10 genes were upregulated and 2 were downregulated after vocal fold dehydration compared with the euhydrated control. Concerning osmotic stress, six genes were upregulated with dehydration only, six genes were upregulated following rehydration with water, whereas a single gene was upregulated with electrolyte rehydration. All genes with significantly different expression between the rehydration groups showed lower expression with electrolytes compared with water. The results support a potential role of oxidative and osmotic stresses in vocal folds related to systemic dehydration. The differences in stress-related gene expression in vocal fold tissue between rehydration with electrolytes or water, albeit modest, suggest that both rehydration options offer clinical utility to subjects experiencing vocal fold dehydration with preliminary evidence that electrolytes may be more effective than water in resolving osmotic stress. NA (prospective animal study) Laryngoscope, 2024.

Histamine deficiency exacerbates cisplatin-induced ferroptosis in cochlea hair cells of HDC knockout mice

Cisplatin (CDDP) is extensively utilized in the management of diverse types of cancers, but its ototoxicity cannot be ignored, and clinical interventions are not ideal. Histidine decarboxylase (HDC) is the exclusive enzyme for histamine synthesis. Anti-histamine receptor drugs are ubiquitously employed in the therapeutics of allergies and gastrointestinal diseases. Yet, the specific role of histamine and its signaling in the inner ear is not fully understood. This study utilized cisplatin treated mice and HEI-OC1 auditory hair cell line to establish a cisplatin-induced ototoxicity (CIO) model. Histidine decarboxylase knockout (HDC−/−) mice and histamine receptor 1 (H1R) antagonist were utilized to investigate the influence of HDC/histamine/H1R signaling on ototoxicity. The results identified HDC and H1R expression in mouse hair cells. Transcriptomics indicated that the expression levels of oxidative stress-related genes in the cochlea of HDC−/− mice increased. Furthermore, histamine deficiency or suppression of H1R signaling accelerated HC ferroptosis, a pivotal factor underlying the aggravation of CIO in vivo and in vitro, conversely, the supplementation of exogenous histamine reversed these deleterious effects. Mechanistically, this study revealed that the malfunction of HDC/histamine/H1R signaling induced upregulation of NRF2 expression, accompanied by the upregulation of ACSL4 and downregulation of GPX4 expression, which are major regulatory factors of ferroptosis. In summary, histamine deficiency may induce hair cell death by regulating the H1R pathway and exacerbate CIO. Our findings have indicated a potential therapeutic target for CIO.

Identification of immune- and oxidative stress-related signature genes as potential targets for mRNA vaccines for pancreatic cancer patients.

Adenocarcinoma of the pancreas (PAAD) is one of the deadliest malignant tumors, and messenger ribonucleic acid vaccines, which constitute the latest generation of vaccine technology, are expected to lead to new ideas for the treatment of pancreatic cancer. The Cancer Genome Atlas-PAAD and Genotype-Tissue Expression data were merged and analyzed. Weighted gene coexpression network analysis was used to identify gene modules associated with tumor mutational burden among the genes related to both immunity and oxidative stress. Differentially expressed immune-related oxidative stress genes were screened via univariate Cox regression analysis, and these genes were analyzed via nonnegative matrix factorization. After immune infiltration analysis, least absolute shrinkage and selection operator regression combined with Cox regression was used to construct the model, and the usefulness of the model was predicted based on the receiver operating characteristic curve and decision curve analysis curves after model construction. Finally, metabolic pathway enrichment was analyzed using gene set enrichment analysis combined with Kyoto Encyclopedia of Genes and Genomes and gene ontology biological process analyses. This model consisting of the ERAP2, mesenchymal-epithelial transition factor (MET), CXCL9, and angiotensinogen (AGT) genes can be used to help predict the prognosis of pancreatic cancer patients more accurately than existing models. ERAP2 is involved in immune activation and is important in cancer immune evasion. MET binds to hepatocyte growth factor, leading to the dimerization and phosphorylation of c-MET. This activates various signaling pathways, including MAPK and PI3K, to regulate the proliferation, invasion, and migration of cancer cells. CXCL9 overexpression is associated with a poor patient prognosis and reduces the number of CD8 + cytotoxic T lymphocytes in the PAAD tumor microenvironment. AGT is cleaved by the renin enzyme to produce angiotensin 1, and AGT-converting enzyme cleaves angiotensin 1 to produce angiotensin 2. Exposure to AGT-converting enzyme inhibitors after pancreatic cancer diagnosis is associated with improved survival. The 4 genes identified in the present study - ERAP2, MET, CXCL9, and AGT - are expected to serve as targets for messenger ribonucleic acid vaccine development and need to be further investigated in depth.

Oxidative stress-related genes score predicts prognosis and immune cell infiltration landscape characterization in breast cancer

BackgroundThe tumor microenvironment (TME) typically experiences oxidative stress (OS), marked by a high level of reactive oxygen species (ROS) that can impact tumor advancement and prognosis by modulating the behavior of tumor cells and various immune cells. Oxidative stress-related genes (OSRG) encompass a range of genes involved in ROS pathways, and their specific roles in breast cancer (BC) necessitate further investigation. MethodsUnivariate Cox analysis was performed on genes linked to the OS pathway in the Gene Set Enrichment Analysis (GSEA) database, leading to the identification of 29 significant OSRG in BC. OSRG was divided into three distinct clusters according to the expression and the OSRG score based on the differentially expressed genes (DEGs) was further calculated by principal component analysis (PCA). The correlation between OSRG score and BC clinical features, mutation characteristics, immune checkpoints and immune cell infiltration was analyzed. Establish a multiariable Cox regression model to predict OSRG score effects on clinical characteristics. ResultsSignificant differences were observed in survival analysis, enriched pathways, and immune infiltration among the three OSRG clusters based on 29 genes. Gene clusters were identified through the final selected 395 DEGs, revealing three distinct OSRG expression patterns. An OSRG score model was constructed using DEGs, demonstrating a significant association between high OSRG score and poor prognosis. Significantly, immune checkpoint-related genes exhibited a notable upregulation in the high OSRG score cohort. Additionally, a positive correlation was observed between the OSRG score and tumor mutation burden (TMB) in BC. The OSRG score holds potential implications for clinical immunotherapy in BC patients, and a nomogram was constructed with robust predictive capability for evaluating patient prognosis. ConclusionsThis study elucidated the features of OSRG within BC TME and their possible prognostic significance, offering valuable insights for the development of more targeted immunotherapy approaches for individuals with BC.

P-094 Genetic variations of antioxidant genes may coordinate with lifestyle to define male fertility: A cross-sectional study with control group

Abstract Study question Are polymorphisms of the oxidative stress-related genes different between infertile men and reproductively healthy men? Does lifestyle contribute to fertility outcomes? Summary answer A strong association between the polymorphisms of two antioxidant genes and sperm quality was identified. The infertile men had higher BMI and alcohol usage. What is known already Antioxidant genes including catalase (CAT), superoxide dismutase (SOD), and nitric oxide synthase (NOS) play a critical role in spermatogenesis and sperm functions, especially in stress-response cell signaling pathways. Polymorphisms of antioxidant genes have been reported to be associated with gene function, hence sperm quality, ultimately affecting male fertility in various cohorts. Body mass index (BMI) is universally considered a marker of health reflecting whole health, nutrition, and lifestyle. Smoking and alcohol consumption expose the body to harmful chemicals and oxidative stress. Here, we examined the polymorphisms of antioxidant genes in Vietnamese men and the link with lifestyle to regulate fertility. Study design, size, duration This cross-sectional study with control group recruited from Hanoi Medical University Hospital from 2018-2020. The participants were divided into two groups regarding semen analysis based on WHO 2010 criteria. The participants gave consent, then were clinically examined, interviewed for lifestyle, and genetically analyzed for antioxidant gene variations. An extra inclusion criterion for the control men was having at least one healthy baby. The exclusion criteria were chromosome aberrations and Y chromosome microdeletion. Participants/materials, setting, methods The control group (N = 85) and infertile group (N = 107) were recruited. Semen analysis was carried out by the CASA instrument based on WHO 2010 criteria. Lifestyle characteristics including exercise (per week), smoking (yes/no), alcohol consumption (the threshold for “yes” was five standard drinks/occasion, at least one occasion/month) were recorded. Four variants SOD1:7958G>A, SOD2:c.47T>C, CAT:-262C>T, and NOS3:-786C>T were analyzed by Sanger sequencing. Pearson’s, Chi-squared (χ2), Wilcoxon rank-sum, ANOVA test, and Bonferroni correction were applied where specifically required. Main results and the role of chance The average age of the two groups was not different (31.96 ± 4.87 vs 31.93 ± 6.3 years old, p = 0.92). The body mass index (BMI) of infertile men was significantly higher than the control (24.84 ± 2.31 vs 23.53 ± 2.55 kg/m2, p = 0.00026). No significant difference was identified regarding exercise and smoking. Notably, 96.26% of infertile men consumed alcohol in comparison with 88.23% of the control (p = 0,034). Genetically, SOD1:7958GA genotype and NOS3:-786CT genotype in the infertility group were significantly higher than in the control, OR = 2.191 (95% CI: 1.226–3.915, p = 0.004) and OR = 3.135 (95% CI: 1.591–6.180, p < 0.001), respectively. The frequency of the SOD2:c.47TC genotype was significantly higher in the male infertility group than in the control (OR = 1.941, 95% CI: 1.063–3.595, p = 0.029). Individuals carrying the SOD1:GA+AA, SOD2:TC+CC, and CAT:CT/TT genotype pattern had an increased risk of male infertility (OR = 7.614, p = 0.007), suggesting that gene-gene interaction plays an important role in male reproduction. To our knowledge, this is the first report worldwide on the association between the SOD1:7958G>A polymorphism and male infertility. Together, the data suggest that antioxidant gene polymorphisms and lifestyle, especially alcohol usage, coordinate to regulate male fertility. Limitations, reasons for caution Direct measurement of oxidative stress in the semen of men having different gene variations would be required to ascertain the link between the polymorphisms of antioxidant genes and fertility. The sample size was relatively small, a larger sample size would be required to accurately represent the Vietnamese population. Wider implications of the findings The findings can assist in infertility diagnosis focusing on the group of higher infertile risk genetic variations. Interventions such as antioxidant supplements would be developed and applied, lifestyle advice would be given specifically for a group having high-risk gene variations to accurately target fertility issues. Trial registration number Not applicable

Sargassum horneri extract fermented by Lactiplantibacillus pentosus SH803 mediates adipocyte metabolism in 3T3-L1 preadipocytes by regulating oxidative damage and inflammation

Sargassum horneri (S. horneri), a brown seaweed excessively proliferating along Asian coastlines, are damaging marine ecosystems. Thus, this study aimed to enhance nutritional value of S. horneri through lactic acid bacteria fermentation to increase S. horneri utilization as a functional food supplement, and consequently resolve coastal S. horneri accumulation. S. horneri supplemented fermentation was most effective with Lactiplantibacillus pentosus SH803, thus this product (F-SHWE) was used for further in vitro studies. F-SHWE normalized expressions of oxidative stress related genes NF-κB, p53, BAX, cytochrome C, caspase 9, and caspase 3, while non-fermented S. horneri (SHWE) did not, in a H2O2-induced HT-29 cell model. Moreover, in an LPS-induced HT-29 cell model, F-SHWE repaired expressions of inflammation marker genes ZO1, IL1β, IFNγ more effectively than SHWE. For further functional assessment, F-SHWE was also treated in 3T3-L1 adipocytes. As a result, F-SHWE decreased lipid accumulation, along with gene expression of adipogenesis markers PPARγ, C/EBPα, C/EBPβ, aP2, and Lpl; lipogenesis markers Lep, Akt, SREBP1, Acc, Fas; inflammation markers IFN-γ and NF-κB. Notably, gene expression of C/EBPβ, IFN-γ and NF-κB were suppressed only by F-SHWE, suggesting the enhancing effect of fermentation on obesity-related properties. Compositional analysis attributed the protective effects of F-SHWE to acetate, an organic acid significantly higher in F-SHWE than SHWE. Therefore, F-SHWE is a novel potential anti-obesity agent, providing a strategy to reduce excess S. horneri populations along marine ecosystems.

Effects of microplastics on reproductive characteristics and mechanisms of the marine rotifer Brachionus plicatilis

Microplastic pollution, especially secondary microplastics (MPs), poses a significant threat to marine ecosystems. Despite its prevalence, the impact of natural-aged MPs on marine organisms, hindered by collection challenges, remains poorly understood. This study focused on 1–3 μm natural-aged MPs collected from Japan's coastal sea, investigating their effects on the rotifer Brachionus plicatilis sensu stricto and its reproductive mechanisms. Rotifers exposed to varying MP concentrations (0, 20, and 200 particles/mL) over 14-day batch cultures exhibited reduced population growth and fertilization rates. Down-regulation of reproductive genes and up-regulation of oxidative stress-related genes were observed, indicating MP-induced disruptions. Enhanced activities of superoxide dismutase and acetylcholinesterase and elevated malondialdehyde levels further emphasized oxidative stress. These findings underscore the detrimental impact of MPs on rotifer reproductivity, shedding light on the underlying mechanisms.

Construction of a drug, miRNA, and transcription factor regulatory network in membranous nephropathy based on oxidative stress-related genes

In this study, oxidative stress-related genes (OSRGs) were used to discover membranous nephropathy (MN) genes, evaluate their biological activities and molecular pathways, and develop regulatory networks for drugs, miRNAs and transcription factors. All 862 differentially expressed genes (DEGs) in the GSE108113 dataset were evaluated using the gene expression matrix. Cross-testing of 437 OSRg in the gene cards revealed 28 DE-OSRG genes. We performed the KEGG and gene ontology enrichment studies. Response to reactive oxygen species, chemical stress, oxidative stress, bound globin-hemoglobin complex, endocytic vesicle lumen, blood microparticles, conjugated globin binding, peroxidase activity and heme binding are the major GO-enriched active DE-OSRGs. As in the KEGG pathway study. After excluding the disconnected genes, 19 DE-OSRGs were introduced into the PPI network, and the top five CDE-OSRGs were found: G6PD, HBB, TP 53, KEAP 1, and PXDN. The ROC curve study shows the CDE-OS.

Unveiling an oxidative stress-linked diagnostic signature and molecular subtypes in preeclampsia: novel insights into pathogenesis

Preeclampsia (PE) is a complex pregnancy disorder characterized by hypertension and organ dysfunction, affecting both maternal and fetal health. Oxidative stress has been implicated in the pathogenesis of PE, but the underlying molecular mechanisms remain poorly understood. In this study, we aimed to identify a diagnostic signature and molecular subtypes associated with oxidative stress in PE to gain novel insights into its pathogenesis. The ssGSEA algorithm evaluated oxidative stress-related pathway scores using transcriptional data from the GSE75010 dataset. Oxidative stress-related genes (ORGs) were co lected from these pathways, and hub ORGs associated with PE were identified using the LASSO and logistic regression models. A nomogram prediction model was constructed using the identified ORGs. Consensus clustering identified two molecular subgroups related to oxidative stress, labeled as C1 and C2, with unique immune characteristics and inflammatory pathway profiles. Seventy ORGs associated with oxidative stress, ce l death, and inflammation-related pathways were identified in PE. EGFR, RIPK3, and ALAD were confirmed as core ORGs for PE biomarkers. The C1 and C2 subgroups exhibited distinct immune characteristics and inflammatory pathway profiles. This study provides novel insights into the role of oxidative stress in PE pathogenesis. A diagnostic signature and molecular subtypes associated with oxidative stress were identified, which may improve understanding, diagnosis, and management of PE.

Antioxidant and osteoinductive properties of organic selenium in microdiets for gilthead seabream (Sparus aurata) larvae

This study investigated the effect of yeast derived selenium (Se) dietary supplementation on larval performance, whole body mineral contents, lipid peroxidation, fatty acid profiles, expression of antioxidants and bone biomarkers genes, mineralization and skeletal anomalies in gilthead seabream (Sparus aurata) larvae. Five experimental microdiets containing 1.4, 6.1, 9.2, 12.0 and 14.0 mg Se/kg diets were fed to triplicate groups of larvae (total length: 7.26 ± 0.83 mm, 30 dph) for 21 days. Larval Se levels increased proportionally to the elevation of dietary Se. Those fed with dietary Se level at 6.1 mg/kg had a higher growth performance than those fed with non-supplemented diet (1.4 mg/kg), then reached a plateau from larvae fed with Se6.1 to Se14 diet although growth was not significantly affected by different diets. In addition, larval survival was not significantly affected. However, larvae fed the lowest Se levels showed a significant increase in lipid peroxidation, the downregulation of antioxidant genes, a reduction in polyunsaturated fatty acids (PUFA) contents and the highest incidence of skeletal anomalies. While increase up to 6.1–12 mg Se/kg, reduced oxidative stress, increased PUFA, vertebral mineralization, up-regulated antioxidant and bone metabolism related genes and contributing to reduce skeletal anomalies of larvae. However, further increase in dietary Se up to 14 mg/kg led to the lowest gpx, cat and alp expressions, in agreement with a lower mineralization. These findings suggest, dietary Se level at 6.1 mg/kg would be the minimum dietary Se level required in microdiets for gilthead seabream larvae. Thus, the study demonstrates the importance of dietary Se for bone metabolism and mineralization due to its antioxidant and osteo-inductive properties.

Bioaccumulation and biological effects of hydrogenated cement particles in the marine bivalve, Mytilusgalloprovincialis

The decommissioning and normal functioning of nuclear facilities can result in the production and release of airborne particles in the environment. Aquatic biota are expected to be exposed to these particles considering that nuclear facilities are often located near water bodies. Aerosols, such as cement dust, can interact with radionuclides as well as with heavy metals, and therefore elicit not only radiological impacts but also chemical toxicity. In the present study, we aimed to determine the effects of hydrogenated cement particles (HCPs) as a first step before evaluating any radiotoxicity of tritiated cement particles in the marine mussels, Mytilus galloprovincialis. Responses at different levels of biological organisation were assessed, including clearance rate (CR), tissue specific accumulation, DNA damage and transcriptional expression of key stress related genes. Acute (5 h) and medium-term, chronic (11 d) exposures to 1000 μg L−1 HCPs showed that bioaccumulation, assessed using Cu as a proxy and determined by inductively coupled plasma mass spectrometry, was time and tissue dependent. The highest levels of Cu were found in the digestive gland (DG) after 11 d. HCP exposure caused changes in the expression of oxidative and other stress-related genes, including mt20 in DG and gst and sod in the gill after 5 h exposure, while an overexpression of hsp70 in the gill was observed after 11 d. Genotoxic effects in haemocytes were observed after 11 d of HCP exposure. Multivariate analysis indicated that oxidative stress is the most probable factor contributing to overall physiological dysfunction. Our results provide a baseline to perform further studies employing tritiated cement particles. Specifically, future work should focus on the DG since only this tissue showed significant bioaccumulation when compared to the negative control.

Unveiling the molecular complexity of proliferative diabetic retinopathy through scRNA-seq, AlphaFold 2, and machine learning.

Proliferative diabetic retinopathy (PDR), a major cause of blindness, is characterized by complex pathogenesis. This study integrates single-cell RNA sequencing (scRNA-seq), Non-negative Matrix Factorization (NMF), machine learning, and AlphaFold 2 methods to explore the molecular level of PDR. We analyzed scRNA-seq data from PDR patients and healthy controls to identify distinct cellular subtypes and gene expression patterns. NMF was used to define specific transcriptional programs in PDR. The oxidative stress-related genes (ORGs) identified within Meta-Program 1 were utilized to construct a predictive model using twelve machine learning algorithms. Furthermore, we employed AlphaFold 2 for the prediction of protein structures, complementing this with molecular docking to validate the structural foundation of potential therapeutic targets. We also analyzed protein-protein interaction (PPI) networks and the interplay among key ORGs. Our scRNA-seq analysis revealed five major cell types and 14 subcell types in PDR patients, with significant differences in gene expression compared to those in controls. We identified three key meta-programs underscoring the role of microglia in the pathogenesis of PDR. Three critical ORGs (ALKBH1, PSIP1, and ATP13A2) were identified, with the best-performing predictive model demonstrating high accuracy (AUC of 0.989 in the training cohort and 0.833 in the validation cohort). Moreover, AlphaFold 2 predictions combined with molecular docking revealed that resveratrol has a strong affinity for ALKBH1, indicating its potential as a targeted therapeutic agent. PPI network analysis, revealed a complex network of interactions among the hub ORGs and other genes, suggesting a collective role in PDR pathogenesis. This study provides insights into the cellular and molecular aspects of PDR, identifying potential biomarkers and therapeutic targets using advanced technological approaches.

Development of a Prognostic Risk Model Based on Oxidative StressRelated Genes for Platinum-Resistant Ovarian Cancer Patients.

Ovarian Cancer (OC) is a heterogeneous malignancy with poor outcomes. Oxidative stress plays a crucial role in developing drug resistance. However, the relationships between Oxidative Stress-related Genes (OSRGs) and the prognosis of platinum-resistant OC remain unclear. This study aimed to develop an OSRGs-based prognostic risk model for platinum-resistant OC patients. Gene Set Enrichment Analysis (GSEA) was performed to determine the expression difference of OSRGs between platinum-resistant and -sensitive OC patients. Cox regression analyses were used to identify the prognostic OSRGs and establish a risk score model. The model was validated by using an external dataset. Machine learning was used to determine the prognostic OSRGs associated with platinum resistance. Finally, the biological functions of selected OSRG were determined via in vitro cellular experiments. Three gene sets associated with oxidative stress-related pathways were enriched (p < 0.05), and 105 OSRGs were found to be differentially expressed between platinum-resistant and - sensitive OC (p < 0.05). Twenty prognosis-associated OSRGs were identified (HR: 0:562-5.437; 95% CI: 0.319-20.148; p < 0.005), and seven independent OSRGs were used to construct a prognostic risk score model, which accurately predicted the survival of OC patients (1-, 3-, and 5-year AUC=0.69, 0.75, and 0.67, respectively). The prognostic potential of this model was confirmed in the validation cohort. Machine learning showed five prognostic OSRGs (SPHK1, PXDNL, C1QA, WRN, and SETX) to be strongly correlated with platinum resistance in OC patients. Cellular experiments showed that WRN significantly promoted the malignancy and platinum resistance of OC cells. The OSRGs-based risk score model can efficiently predict the prognosis and platinum resistance of OC patients. This model may improve the risk stratification of OC patients in the clinic.

Terbuthylazine induces oxidative stress and mitophagy through activating cGAS-STING pathway in chicken jejunum

Terbuthylazine (TBA) is a widely employed pesticide that has been found to be a significant source of food and environmental pollution. Excessive exposure to TBA raises considerable apprehension regarding its potential impact on biological health, but its underlying toxic mechanisms have not been reported. Our findings indicated that TBA exposure could cause intestinal damage, as evidenced by decrease in the quantity of cupped cells and decrease in the expression of intestinal barrier-related proteins (Claudin-1, Occludin, ZO-1, and JAM-1). Additionally, exposure to TBA resulted in a significant decrease in the expression levels of oxidative stress-related genes and proteins. Furthermore, the expression of 8-hydroxy-2′-deoxyguanosine was significantly upregulated. Additionally, excessive exposure to TBA led to a substantial release of mitochondrial DNA, which further activated the cGAS-STING pathway and caused TBK1 and IRF3 phosphorylation. Meanwhile, mitophagy was activated under TBA exposure, as evidenced by decrease in the protein and gene levels of p62 and increase in the levels of PINK1, PARKIN and LC3 II. Therefore, our results suggested that TBA exposure induced oxidative stress in the jejunum and caused mtDNA leakage, for activating the cGAS-STING pathway, which in turn promoted mitophagy. These findings revealed the toxicity mechanisms of TBA, which provided new insights into food safety caused by pesticide contamination.

Identification and validation of oxidative stress-related genes in sepsis-induced myopathy.

Sepsis-induced myopathy (SIM) a complication of sepsis that results in prolonged mechanical ventilation, long-term functional disability, and increased patient mortality. This study was performed to identify potential key oxidative stress-related genes (OS-genes) as biomarkers for the diagnosis of SIM using bioinformatics. The GSE13205 was obtained from the Gene Expression Omnibus (GEO) database, including 13 SIM samples and 8 healthy samples, and the differentially expressed genes (DEGs) were identified by limma package in R language. Simultaneously, we searched for the genes related to oxidative stress in the Gene Ontology (GO) database. The intersection of the genes selected from the GO database and the genes from the GSE13205 was considered as OS-genes of SIM, where the differential genes were regarded as OS-DEGs. OS-DEGs were analyzed using GO enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and protein-protein interaction (PPI) networks. Hub genes in OS-DEGs were selected based on degree, and diagnostic genes were further screened by gene expression and receiver operating characteristic (ROC) curve. Finally, a miRNA-gene network of diagnostic genes was constructed. A total of 1089 DEGs were screened from the GSE13205, and 453 OS-genes were identified from the GO database. The overlapping DEGs and OS-genes constituted 25 OS-DEGs, including 15 significantly upregulated and 10 significantly downregulated genes. The top 10 hub genes, including CD36, GPX3, NQO1, GSR, TP53, IDH1, BCL2, HMOX1, JAK2, and FOXO1, were screened. Furthermore, 5 diagnostic genes were identified: CD36, GPX3, NQO1, GSR, and TP53. The ROC analysis showed that the respective area under the curves (AUCs) of CD36, GPX3, NQO1, GSR, and TP53 were 0.990, 0.981, 0.971, 0.971, and 0.971, which meant these genes had very high diagnostic values of SIM. Finally, based on these 5 diagnostic genes, we found that miR-124-3p and miR-16-5p may be potential targets for the treatment of SIM. The results of this study suggest that OS-genes might play an important role in SIM. CD36, GPX3, NQO1, GSR, and TP53 have potential as specific biomarkers for the diagnosis of SIM.

Identifying Oxidative Stress-Related Genes (OSRGs) as Potential Target for Treating Periodontitis Based on Bioinformatics Analysis.

Periodontitis (PD) is a multifactorial inflammatory disease that is closely associated with periodontopathic bacteria. Numerous studies have demonstrated oxidative stress (OS) contributes to inflammation and is a prime factor in the development of PD. It is imperative to explore the function of newly discovered hub genes associated with OS in the advancement of PD, thereby identifying potential targets for therapeutic intervention. The goal of the current study was to identify the oxidative -stress-related genes (OSRGs) associated with periodontitis (PD) development using an integrated bioinformatics method. DEGs from GEO gene-expression data were identified using the "limma" package. We obtained OSRGs from GeneCards and utilized a Venn diagram to uncover differentially expressed OSRGs (DEOSRGs). After receiving the DEOSRGs, we employed Gene Ontology (GO), Kyoto Encyclopaedia of Genes and Genomes (KEGG), and protein-protein interaction (PPI) analytical tools to examine their possible functions and pathways in PD. Receiver operating characteristic (ROC) curves screened for hub genes of PD. RT-qPCR and western blot analysis were used to detect DEOSRG expression in mouse ligature-induced periodontitis gingival tissues. The investigation identified 273OSRGs. Based on PPI analysis, we recognized 20 OSRGs as hub genes. GO and KEGG enrichment analysis indicated that these hub genes were predominantly enriched in leukocyte migration, lymphocyte proliferation, and humoral immune response, and associated with leukocyte trans-endothelial migration, cytokine-cytokine receptor interaction, and NF-κB signaling pathway. Following ROC analysis, VCAM1, ITGAM, FCGR3A, IL1A, PECAM1, and VCAM1were identified as PD prognostic gene. RT-qPCR and western blot analyses confirmed that the expression ITGAM, FCGR3A, and PECAM1 were significantly elevated in the gingival tissues obtained from mice. This investigation revealed that ITGAM, FCGR3A, and PECAM1 may have a crucial function in the advancement of PD.

Up-regulation of inflammatory, oxidative stress, and apoptotic mediators via inflammatory, oxidative stress, and apoptosis-associated pathways in bovine endometritis

Endometritis is the inflammation of the endothelial lining of the uterine lumen and is multifactorial in etiology. Escherichia (E.) coli is a Gram-negative bacteria, generally considered as a primary causative agent for bovine endometritis. Bovine endometritis is characterized by the activation of Toll-like receptors (TLRs) by E. coli, which in turn triggers inflammation, oxidative stress, and apoptosis. The objective of this study was to investigate the gene expression of inflammatory, oxidative stress, and apoptotic markers related to endometritis in the uteri of cows. Twenty uterine tissues were collected from the abattoir. Histologically, congestion, edema, hyperemia, and hemorrhagic lesions with massive infiltration of neutrophil and cell necrosis were detected markedly (P < 0.05) in infected uterine samples. Additionally, we identify E. coli using the ybbW gene (177 base pairs; E. coli-specific gene) from infected uterine samples. Moreover, qPCR and western blot results indicated that TLR2, TLR4, proinflammatory mediators, and apoptosis-mediated genes upregulated except Bcl-2, which is antiapoptotic, and there were downregulations of oxidative stress-related genes in the infected uterine tissue. The results of our study suggested that different gene expression regimes related to the immune system reflex were activated in infected uteri. This research gives a novel understanding of active immunological response in bovine endometritis.

Cytochrome P450 CYP736A12 is crucial for Trichoderma asperellum-induced alleviation of phoxim phytotoxicity and reduction of pesticide residue in tomato roots

Trichoderma can enhance the metabolism of organophosphate pesticides in plants, but the mechanism is unclear. Here, we performed high-throughput transcriptome sequencing of roots upon Trichoderma asperellum (TM) inoculation and phoxim (P) application in tomato (Solanum lycopersicum L.). A total of 4059 differentially expressed genes (DEGs) were obtained, including 2110 up-regulated and 1949 down-regulated DEGs in P vs TM+P. COG and KOG analysis indicated that DEGs were mainly enriched in signal transduction mechanisms. We then focused on the pesticide detoxification pathway and screened out cytochrome P450 CYP736A12 as a putative gene for functional analysis. We suppressed the expression of CYP736A12 in tomato plants by virus-induced gene silencing and analyzed tissue-specific phoxim residues, oxidative stress markers, glutathione pool, GST activity and related gene expression. Silencing CYP736A12 significantly increased phoxim residue and induced oxidative stress in tomato plants, by attenuating the TM-induced increased activity of antioxidant and detoxification enzymes, redox homeostasis and transcripts of detoxification genes including CYP724B2, GSH1, GSH2, GR, GPX, GST1, GST2, GST3, and ABC. The study revealed a critical mechanism by which TM promotes the metabolism of phoxim in tomato roots, which can be useful for further understanding the Trichoderma-induced xenobiotic detoxification and improving food safety.

Immune cell infiltration and drug response in glioblastoma multiforme: insights from oxidative stress-related genes

BackgroundGBM, also known as glioblastoma multiforme, is the most prevalent and lethal type of brain cancer. The cell proliferation, invasion, angiogenesis, and treatment of gliomas are significantly influenced by oxidative stress. Nevertheless, the connection between ORGs and GBM remains poorly comprehended. The objective of this research is to investigate the predictive significance of ORGs in GBM and their potential as targets for therapy.MethodsWe identified differentially expressed genes in glioma and ORGs from public databases. A risk model was established using LASSO regression and Cox analysis, and its performance was evaluated with ROC curves. We then performed consistent cluster analysis on the model, examining its correlation with immunity and drug response. Additionally, PCR, WB and IHC were employed to validate key genes within the prognostic model.Results9 ORGs (H6PD, BMP2, SPP1, HADHA, SLC25A20, TXNIP, ACTA1, CCND1, EEF1A1) were selected via differential expression analysis, LASSO and Cox analysis, and incorporated into the risk model with high predictive accuracy. Enrichment analyses using GSVA and GSEA focused predominantly on malignancy-associated pathways. Subtype C of GBM had the best prognosis with the lowest risk score. Furthermore, the model exhibited a strong correlation with the infiltration of immune cells and had the capability to pinpoint potential targeted therapeutic medications for GBM. Ultimately, we selected HADHA for in vitro validation. The findings indicated that GBM exhibits a significant upregulation of HADHA. Knockdown of HADHA inhibited glioma cell proliferation and diminished their migration and invasion capacities and influenced the tumor growth in vivo.ConclusionThe risk model, built upon 9 ORGs and the identification of GBM subtypes, suggests that ORGs have a broad application prospect in the clinical immunotherapy and targeted drug treatment of GBM. HADHA significantly influences the development of gliomas, both in vivo and in vitro.

CircBCL2L13 attenuates cardiomyocyte oxidative stress and apoptosis in cardiac ischemia‒reperfusion injury via miR-1246/PEG3 signaling.

Ischemia‒reperfusion (I/R) is a common complication in the clinical treatment of acute myocardial infarction (MI), in which cardiomyocytes play a pivotal role in the recovery of cardiac function after reperfusion injury. The expression of numerous circular ribonucleic acids (circRNAs) is disrupted in I/R-induced cardiac damage, but the potential role of circRNAs in I/R damage has not been fully elucidated. The purpose of the present study was to clarify the biological action and molecular mechanism of circRNA 002166 (also termed circCL2L13) in postmyocardial I/R. Oxygen-glucose deprivation/reoxygenation (OGD/R) in an in vivo model was performed to simulate I/R damage. real-time polymerase chain reaction analysis was also conducted to evaluate the relationships of the SOD1, SOD2, NRF2, HO1 and GPX4 indicators with oxidative stress injury. TUNEL immunofluorescence was used to evaluate the degree of cardiomyocyte apoptosis in the different treatment groups. The circBCL2L13 level was markedly upregulated in myocardial tissues from a mouse I/R model. Overexpression of circBCL2L13 markedly attenuated the expression of oxidative stress-related genes and apoptosis in OGD/R-induced cardiomyocytes. A mechanistic study revealed that circBCL2L13 functions as a ceRNA for miR-1246 and modulates paternally expressed gene 3 (PEG3). Eventually, circBCL2L13 was proven to regulate PEG3 by targeting miR-1246, thereby protecting against OGD/R-induced cardiomyocyte oxidative damage and apoptosis. In conclusion, our study confirmed that the circBCL2L13/miR-1246/PEG3 axis suppressed the progression of OGD/R injury in cardiomyocytes, which might lead to new therapeutic strategies for cardiac I/R injury.