Ferulic acid, a common dietary phenolic abundant in plant cell walls, has been identified as a potential drug candidate with radiation-protective effects in experimental models. This review summarizes new developments regarding the molecular mechanisms, experimental models and translational potential of ferulic acid-induced radioprotection. Mechanistically, ferulic acid attenuates ionizing radiation-induced damage by scavenging free radicals, inhibiting lipid peroxidation, maintaining mitochondrial fitness, modulating inflammation signaling pathways and upregulating endogenous antioxidant systems partially through nuclear translocation of the Nrf2 pathway. Preclinical studies across in vitro (human and animal cell lines), ex vivo (human blood chromosomal aberration, micronucleus, and γ-H2AX assays), and in vivo rodent models consistently show that ferulic acid reduces DNA damage and chromosomal alterations, supports cell survival pathways, and, in some conditions, enhances DNA repair, translating into improved tissue histology, hematopoietic recovery, and post-irradiation survival. Despite promising efficacy signals, there are still issues with pharmacokinetics, optimal dosing schedules, long-term safety/adverse events, and bioavailability in humans. This review discusses the priority directions for translation: (1) systematic pharmacokinetic and toxicology profiling, (2) discovery of ferulic acid derivatives and delivery systems (e.g. nanoparticles, prodrugs) that facilitate tissue targeting, and (3) rigorous clinical trials in prophylactic and post-exposure settings, with combination strategies involving established radioprotectors. Bridging preclinical mechanistic insights with rigorous clinical evaluation could position ferulic acid as a safe, low-cost, and widely accessible radioprotective adjunct suitable for both medical and occupational applications.
Thioacetamide (TAA) induces renal injury via oxidative stress and inflammation. Remogliflozin (Remo), an SGLT2 inhibitor, was evaluated for potential renoprotection. Twenty-four male Wistar rats were assigned to control, TAA (100 mg/kg IP twice weekly), TAA + Remo 25 mg/kg, or TAA + Remo 50 mg/kg (oral daily). Outcomes included renal function, oxidative stress (GSH, SOD, MDA), antioxidant biomarkers (Nrf2, HO-1), inflammatory mediators (TLR4/NF-κB, TNF-α, IL-1β), metabolic/kinase biomarkers (SIRT1, AMPK, PI3K, AKT), and histopathology/immunohistochemistry (mTOR, MYD88, Nrf2). Remogliflozin was associated with lower serum creatinine, urea, and uric acid, with endpoint-specific differences between doses. Remo was associated with higher renal Nrf2, HO-1, SIRT1, and p-AMPK, and lower MDA, TLR4, NF-κB, TNF-α, IL-1β, PI3K, and AKT. Histopathology and IHC showed associations with reduced tissue injury, lower mTOR and MYD88 immunoreactivity, and increased Nrf2 staining. While the 50 mg/kg group showed changes in more markers, this does not establish uniform dose superiority or a formal dose-response relationship; at 25 mg/kg, effects differed among AMPK-related endpoints. Direct 25-versus-50 mg/kg comparisons were included in the Tukey-Kramer analysis for each endpoint. No pharmacokinetic measurements or formal dose-response analyses were performed. In this exploratory model, remogliflozin was associated with attenuation of TAA-induced renal injury and modulation of related biomarkers. Causal mechanisms remain to be confirmed by targeted intervention studies. Findings are limited to young male Wistar rats and should not be generalized to other populations or clinical settings. Remogliflozin warrants further preclinical investigation in TAA-associated renal injury.
Atrazine (ATR) is a globally used herbicide with a long environmental half-life, resulting in its widespread persistence in various environmental media. ATR has been recognized as an environmental endocrine disruptor. The thyroid gland, the largest endocrine organ in the human body, regulates essential physiological processes, including metabolism, growth, and development, through the secretion of thyroid hormones. Accumulating evidence indicates that ATR can adversely affect thyroid function through multiple pathways, including disruption of the hypothalamic-pituitary-thyroid axis, interference with thyroid hormone synthesis and metabolism, and induction of oxidative stress. This review aims to comprehensively summarize the effects of ATR on thyroid morphology and function, as well as its potential toxicological mechanisms. It also seeks to provide references for a deeper understanding of ATR-induced thyroid toxicity and to offer a scientific basis for the development of relevant risk assessment and prevention strategies.
The blood-brain barrier (BBB) is primarily regulated by highly selective endothelial cells. Inflammation of the brain capillaries can compromise the BBB's functioning. Methylprednisolone (M-Pred), a synthetic glucocorticoid, is clinically prescribed to treat systemic inflammation; however, little is known about its effect on both non-inflamed and inflamed brain capillaries. This study evaluated the effectiveness of M-Pred in ameliorating the lipopolysaccharide (LPS)-induced inflammatory response using the in vitro BBB model (bEnd.3). Cultured brain endothelial cells (BECs) were exposed to LPS (500, 1000, 2000 ng/ml) and co-treated with selected concentrations of M-Pred (10, 20, 40 µM). Cell proliferation, quantification of pro-inflammatory cytokines TNF-α and IL-1β (ELISA), and monolayer permeability (Transendothelial Electrical Resistance) were investigated. LPS decreased live cell number, increased dead cell number, and increased cell monolayer permeability; LPS increased pro-inflammatory cytokine secretion. These data confirmed the experimental functionality of the in vitro inflammatory BBB model. In the absence of inflammation, M-Pred decreased bEnd.3 cell monolayer permeability and pro-inflammatory cytokine secretion. M-Pred failed to alleviate LPS-induced inflammation across all tested concentrations. Chronic M-Pred treatment in the absence of inflammation proved detrimental to bEnd.3 cells' physiology.
Drug safety remains a central challenge in drug development and post-marketing surveillance, as the limited size and duration of pre-approval trials constrain detection of rare or delayed adverse effects, leaving patients exposed to residual risk after launch. Using ProTox 3.0 in silico toxicity predictions and statistical modeling, we analyzed an observational cohort of nearly 2,000 historically marketed small-molecule drugs and identified hepatotoxicity as a robust and consistent determinant of pharmaceutical post-marketing withdrawal probability after adjustment for therapeutic context. Other organ toxicities and structural descriptors of the drug molecules exhibited additional, indication-specific associations with withdrawal status, indicating that ex-ante toxicity liability is heterogeneous across therapeutic areas. While our analysis does not establish causality, the stable correlations observed across toxicity profiles, structural characteristics, and clinical indications suggest that a substantial fraction of withdrawal risk is statistically predictable. Embedding these quantitative risk signals into early-stage decisions and targeted safety evaluation strategies offers a data-driven approach to reduce late-stage attrition and post-marketing withdrawals, thereby contributing to safer and more efficient drug development.
OBJECTIVE:Compare the effectiveness of machine learning algorithms and traditional logistic regression in predicting the mortality risk of young patients with acute poisoning, and establish a risk stratification nomogram. METHODS:This multicenter retrospective study derived a derivation cohort of 406 young adults with acute poisoning from Wenzhou and an external validation cohort of 150 patients from Lishui. LASSO regression was used to screen predictive factors from 43 candidate variables. Compare the predictive performance of 14 machine learning algorithms (including RandomForest, XGBoost, CatBoost, LightGBM, SVM, etc.) with logistic regression on a training set (7:3 random split). The model evaluation indicators include AUC, sensitivity, specificity, and calibration, and conduct internal and external verification. RESULTS:LASSO identified six independent predictive factors: white blood cell count, creatinine, herbicide poisoning, invasive mechanical ventilation, liver dysfunction, and shock. The discriminative power of the final logistic regression is comparable to that of the optimal machine learning model (internal validation AUC 0.885, external validation AUC 0.971), and it is well calibrated (Brier score 0.058-0.082, Hosmer Lemeshow test p > 0.05). A nomogram for predicting the 28-day mortality risk of young patients was constructed based on Logistic regression. CONCLUSION:Logistic regression performs similarly to complex machine learning algorithms in predicting the risk of death from acute poisoning in young adults, with better interpretability and clinical practicality. The nomogram constructed based on this is a simple and effective early risk stratification tool, which can serve as one of the reference tools for clinical decision-making assistance.
Genotoxicity is a fundamental biological process linked to the development of numerous diseases, particularly cancer, due to its impact on the integrity and stability rof genetic material. In this context, natural compounds with antigenotoxic properties have gained increasing attention as potential agents for preventing or mitigating DNA damage. Species of the genus Lippia (Verbenaceae) have emerged as a relevant source of bioactive metabolites with promising genoprotective effects. This review provides a comprehensive analysis of the antigenotoxic activity of Lippia spp., focusing on key species such as Lippia alba, Lippia citriodora, Lippia graveolens, and Lippia sidoides. Special emphasis is placed on their phytochemical composition, particularly flavonoids and phenolic acids, including quercetin, luteolin, apigenin, caffeic acid, and rosmarinic acid, which are responsible for their biological activity. Evidence from in vitro and in vivo studies indicates that Lippia extracts exhibit low genotoxic potential and can reduce DNA damage induced by chemical and physical agents. The molecular mechanisms underlying these effects involve reactive oxygen species scavenging, activation of endogenous antioxidant systems, modulation of DNA repair pathways, metal chelation, and regulation of cellular signaling and epigenetic processes. Additionally, potential applications in chemoprevention, environmental health, and nutraceutical development are discussed. Overall, Lippia species represent a valuable source of natural antigenotoxic compounds; however, further studies in complex biological models and clinical settings are required to validate their efficacy, safety, and applicability in human health.
The functional nutraceutical Spirulina (SP) was evaluated against alcohol intoxication in mice livers, concurrently striving to elucidate its protective mechanisms in cellular death pathways: necroptosis and pyroptosis. Ethanol (ET) intoxication was induced via intake of 5% ethanol in drinking water for 10 days, succeeded by a substantial dose of 50% ethanol (4 g/kg, i.p.) on day 11. SP (250 and 300 mg/kg, p.o.) were administered to the ET-intoxicated mice one hour prior to ethanol consumption for 11 days. The two submaximal doses effectively modulated the ET-instigated hepatic abnormalities. Both doses restored the disrupted hepatic function and architecture. SP mitigated serum liver biomarkers: ALT, AST and ALP, in addition to improving survival. SP substantially modified hepatic oxidative stress by inhibiting the lipid peroxidation product MDA and elevating the antioxidant levels of SOD and GSH. Meanwhile, SP counteracted the ET-induced elevated levels of hepatic TNF-α, the necroptosis-related molecular signals; RIPK1/RIPK3/MLKL and the pyroptosis biomarkers: NLRP3/caspase-1/IL-1β. However, no extra benefit was detected with the higher dose. These findings robustly imply the hepatoprotective properties of Spirulina in alcoholism at a dose correspondent to 250 mg/kg via revoking hepatic cell death chains: necroptosis and pyroptosis. Thereby, opens a new avenue for assisting cellular repair mechanisms.
Following the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) multidisciplinary guideline M7 (R2), in silico prediction, in vitro and in vivo genotoxicity evaluations were used to evaluate the potential genotoxic risk of (-)-scopolamine hydrobromide trihydrate (SHT), the main impurity of scopolamine butylbromide in the Chinese Pharmacopeia (ChP). The 2018 in silico models for genotoxicity (Derek Nexus and Sarah Nexus) predicted SHT to be a Class 4 impurity. Subsequent in vitro and in vivo genotoxicity tests (bacterial reverse mutation test, in vitro mammalian chromosomal aberration test, in vitro mammalian cell gene mutation test and mammalian erythrocyte micronucleus test) showed no positive findings, indicating that SHT has no evidence of genotoxic potential under the tested conditions. Therefore, SHT could be tentatively categorized as a Class 5 impurity according to the ICH multidisciplinary guideline M7 (R2), with a threshold according to ICH quality guideline Q3B (R2). In silico prediction in 2026 confirmed this classification, demonstrating the high reliability of the Nexus software database for classification according to ICH multidisciplinary guideline M7 (R2). In the ChP, the SHT threshold in scopolamine butylbromide falls between the identification thresholds and the qualification thresholds of ICH quality guideline Q3B (R2), which is accurate and reasonable.
Vancomycin (VM) therapy is one of the cornerstone options in the treatment of resistant Gram-positive bacterial infections. However, its drawback is associated with the side effect hepatotoxicity during optimal high doses. It is unknown whether quercetin (Que), a natural bioactive flavonoid, could protect the liver against VM-induced hepatotoxicity. The study thus aimed to explore the potential protective effects of Que on VM-induced hepatotoxicity in male Wistar rats. Rats were randomized into groups and administered VM (200 mg/kg body weight, twice a day) and/or Que (100 mg/kg body weight) for 7 consecutive days. The VM injection induced liver dysfunction revealed via significantly elevated serum activities of ALT, AST, and GGT compared to the control group (p < 0.001). VM markedly decreased hepatic activities of SOD, CAT and GPx, while MDA level increased compared to the control group (p < 0.001). Additionally, VM increased TNF-α levels while decreasing IL-10 levels. There were considerable increases in the hepatic expression of caspase-3, NF-κB, Keap1, NOX4, 4-HNE and NLRP3, whereas the expression of HO1, Nrf2, PI3K, p-Akt decreased significantly as revealed by qRT-PCR and immunohistochemical analyses (p < 0.001). Interestingly, the Que administration attenuated the VM-induced alterations on the liver enzymes and antioxidant enzymes, including the MDA and 4-HNE. Que exerted prominent modulatory effects on the mechanistic proteins and mRNA expression in a manner comparable to the control. Overall, the present findings suggest that quercetin may mitigate vancomycin-induced hepatotoxicity in rats by modulating oxidative stress, inflammatory signaling, and apoptosis-related pathways.
Per- and polyfluoroalkyl substances (PFAS) are persistent surfactants with ingestion as a major exposure route, positioning the intestine as a primary site of contact. This narrative review integrates mechanistic toxicology, multi-omics microbiology, and human observational studies to evaluate whether PFAS-associated disruption of intestinal homeostasis could contribute to colorectal cancer (CRC). In vitro epithelial systems and animal models indicate that selected PFAS can impair barrier function through altered membrane properties and reduced tight-junction expression, increasing paracellular permeability and luminal antigen translocation. PFAS may also perturb goblet-cell secretion and mucus organization, in part through endoplasmic reticulum (ER) stress and altered autophagy, thereby facilitating mucosa-associated bacterial adherence. Stress signaling can converge on mitochondrial dysfunction and reactive oxygen species (ROS) generation that primes inflammasome activity and cytokine-mediated inflammation. In colon cell models, PFOA and PFOS have been associated with modulation of Wnt/β-catenin signaling and downstream transcriptional programs linked to proliferative and invasive phenotypes. At the community level, exposure-associated dysbiosis includes loss of butyrate-producing taxa and disruption of bile acid pools, consistent with reduced short-chain fatty acids (SCFAs) and altered farnesoid X receptor signaling. However, epidemiologic findings remain inconsistent, including null and inverse associations that may reflect reverse causation from occult bleeding, exposure misclassification, residual dietary confounding, non-monotonic dose responses, congener heterogeneity, and species-specific toxicokinetics. We propose priorities for future work including long-lag prospective sampling, physiologically based pharmacokinetic (PBPK)-informed exposure reconstruction, and adverse outcome pathway (AOP)-anchored multi-omics endpoints for causal inference and regulation.
Electronic cigarettes are widely used by individuals in their reproductive years, yet polymer materials in pods, wicks, seals, and casings remain underexamined as possible contributors to inhaled particulate exposure. This narrative review evaluates whether e-cigarette device components could plausibly generate microplastics or nanoplastics during use and whether such particles, if present, could have reproductive relevance. Evidence from device-material studies, polymer degradation chemistry, aerosol physics, inhalation toxicology, and reproductive microplastic models was synthesized. Current devices place polycarbonate, polydimethylsiloxane, nylon, and other polymers near heating and aerosolization zones, where thermal cycling, solvent contact, and mechanical stress could theoretically promote oxidation, chain scission, embrittlement, or fragmentation. However, no study has chemically identified or quantified device-derived microplastics or nanoplastics in e-cigarette aerosols using polymer-resolving methods. Thus, links between e-cigarette use, inhaled polymer particles, and reproductive harm remain hypothetical. Evidence from non-e-cigarette models shows that micro- and nanoplastics can induce oxidative stress, inflammation, endocrine disruption, barrier interaction, and cellular injury, but these findings cannot be extrapolated without confirming particle formation, polymer identity, dose, and biodistribution. Future research should prioritize polymer-resolved aerosol testing under realistic puffing regimens, including unused and aged devices, e-liquids, condensates, and emitted aerosols. Key endpoints should include polymer identity, particles per puff, particles per mL of e-liquid consumed, particle size distribution, polymer mass, pulmonary deposition, systemic translocation, and reproductive or placental effects. Device-derived microplastics should be treated as a plausible particle-safety concern requiring direct experimental evaluation.
Cisplatin resistance remains a major limitation in the treatment of oral squamous cell carcinoma (OSCC), often associated with altered oxidative stress. This study aimed to evaluate whether matrine can enhance cisplatin sensitivity in OSCC cells and explore its potential underlying mechanisms.Bioinformatics analysis and molecular docking were used to predict potential targets and pathways. In vitro experiments were conducted using CAL27 and cisplatin-resistant CAL27/DDP cells. Cell viability was assessed by CCK-8 assay, and drug interaction was evaluated using combination index (CI). Colony formation, reactive oxygen species (ROS), glutathione (GSH), apoptosis, and protein expression were analyzed.A total of 104 matrine-related targets and 21 overlapping genes were identified. Enrichment analysis suggested that oxidative stress-related pathways may be involved. Matrine alone showed limited cytotoxicity, while it significantly enhanced cisplatin sensitivity, reducing IC50 from 8.340 μM to 2.703 μM (p < 0.01) with CI values <1. Combined treatment decreased GSH and increased ROS (p < 0.001), accompanied by increased apoptosis (p < 0.001). The expression of Nrf2-related antioxidant proteins was reduced, while apoptotic protein levels were increased.Matrine enhances cisplatin sensitivity in OSCC cells, which may be associated with the regulation of oxidative stress and apoptosis. These findings suggest that matrine may serve as a potential chemosensitizing agent.
Etoxazole (ETX) is a widely used organofluorine acaricide/insecticide applied to many food crops, and its residues have been detected in food matrices at levels of concern for human dietary exposure. However, its hepatotoxic and nephrotoxic potential following subchronic oral exposure remains insufficiently characterized. This study investigated the dose-dependent effects of repeated oral ETX administration on serum biochemical parameters, hepatic and renal antioxidant enzyme activities, lipid peroxidation, and histopathological features in Wistar albino rats. Six groups of seven female rats each received normal control (NC) or ETX at 25, 100, 250, 500, or 750 mg/kg/day by gavage for 28 consecutive days. At the end of the exposure period, serum parameters (AST, ALT, ALP, GGT, creatinine, uric acid, glucose, total cholesterol, triglycerides, HDL, LDL), catalase (CAT), glutathione S-transferase (GST), reduced glutathione (GSH), and malondialdehyde (MDA) levels in liver and kidney tissues, and histopathological changes were evaluated. ETX caused significant, dose-dependent increases in AST and ALT from ETX100, in ALP and GGT from ETX500, and in creatinine and uric acid at higher doses, indicating progressive hepatic and renal injury. Hepatic and renal CAT, GST, and GSH activities significantly decreased, whereas MDA levels significantly increased in the higher-dose groups, demonstrating oxidative stress-mediated disruption of antioxidant defenses. Histopathological evaluation revealed dose-dependent liver injury and significant tubular damage in kidneys. The tentative NOAEL and LOAEL were estimated at 25 and 100 mg/kg/day, respectively. These findings demonstrate that ETX induces dose-dependent hepatorenal toxicity in rats through an oxidative stress-mediated mechanism and provide relevant data for dietary risk assessment.
Acetaminophen (i.e. paracetamol; APAP) overdose is the most common cause of acute liver injury in the United States, yet outcomes range from recovery to acute liver failure (ALF), defined by coagulopathy and hepatic encephalopathy (HE). Clinical decision-making is difficult because routine indices of hepatocellular injury (e.g. ALT/AST) do not reliably predict which patients will recover versus progress to ALF. This underscores the need to define mechanisms that drive progression to ALF and to discover biomarkers that better predict clinical trajectory. A major barrier is the lack of an experimentally tractable model in which severe hepatocellular injury is comparable, but neurological outcome diverges-a defining feature of human APAP toxicity. To address this, we established APAP dosing conditions in mice that produce similar peak liver injury yet distinct clinical courses. Mice treated with 300 mg/kg or 500 mg/kg APAP exhibited comparable increases in ALT and hepatic necrosis. In contrast, only 500 mg/kg APAP caused robust neurological dysfunction consistent with HE, including impaired reflex integrity and motor coordination, accompanied by cerebral edema and reduced cerebral blood flow. Hyperammonemia is widely implicated in HE, but ammonia levels do not always track with HE severity in patients, suggesting additional cooperating factors. Consistent with this clinical discordance, blood ammonia increased to a similar extent in both dosing groups despite clear divergence in neurological impairment. Together, these findings establish a patient-relevant platform that dissociates hepatocellular necrosis (and hyperammonemia) from HE, enabling identification of mediators that drive neurovascular dysfunction and the transition from severe liver injury to ALF.
Hyperoside (HYP), a plant-derived flavonoid, was evaluated for its cytotoxic, anti-cancer, genotoxic, antigenotoxic, and antioxidant properties, and potential mechanisms of action using an integrated in vitro and in silico approach. Cytotoxicity and anti-cancer activities were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in CCD18-Co healthy colon epithelial and DLD-1 colon cancer cells. At the same time, genotoxicity and antigenotoxicity potentials were examined in human lymphocytes using COMET assay. Antioxidant activity was determined by 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay, and molecular docking was performed with key regulatory proteins (p53, ATM, 7O7B, and Keap1), and in silico toxicity profiling was conducted using the Percepta platform. HYP selectively reduced the viability of colon cancer cells (43.43%-70.24%) without inducing cytotoxicity in healthy colon epithelial cells (cell viability percentage ranging from 82.25% to 111.88%) after 24 and 48 h of exposure. HYP did not significantly increase DNA damage at 7.81-62.5 μg/mL; however, it exhibited antigenotoxic effects at all concentrations, significantly reducing H2O2-induced DNA damage. HYP also showed significant antioxidant activity, with DPPH inhibition ranging from 53.09% to 78.64%. Docking analyses revealed strong binding affinities for ATM and Keap1, supporting its potential role in modulating oxidative stress and DNA damage response pathways. Percepta-based toxicity profiling predicted low to moderate acute systemic toxicity, limited oral bioavailability, and no major cardiotoxic or CYP-mediated safety liabilities; notably, predicted mutagenicity alerts were not corroborated by in vitro DNA damage assessments. Overall, these findings suggest that HYP exhibits selective anticancer and antigenotoxic properties, potentially mediated by its antioxidant activity.
INTRODUCTION:Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of chronic myeloid leukemia (CML); however, TKI resistance remains a persistent challenge. This study investigates the effects of zingerone on CML cell growth and nilotinib resistance. METHODS:K562 and LAMA84 cells were treated with zingerone (5-100 μM) or nilotinib (1-50 nM), and cytotoxicity was assessed using cell counting Kit-8 assay. Nilotinib-resistant cells (K562R, LAMA84R) were generated through gradual exposure to increasing nilotinib concentrations (1-10 nM) over six months. Subsequently, cells were treated with 10 μM zingerone and/or 5 nM nilotinib. Cell survival and apoptosis were measured by Trypan blue staining and flow cytometry. Protein levels of Bcr-Abl, apoptotic markers and PI3K pathway components were analyzed by Western blotting. RESULTS:Zingerone, nilotinib and their combination reduced parental CML cell survival and increased apoptosis. Resistant cells showed no significant response to nilotinib alone, confirming acquired resistance. However, the addition of zingerone markedly reduced survival and increased apoptosis in these resistant cells. The combination of zingerone and nilotinib increased levels of cleaved PARP, cleaved caspase-3, -9 and -8, while decreasing Bcl-2. Zingerone alone or in combination with nilotinib also reduced phosphorylation of PI3K, AKT and mTOR in resistant cells. CONCLUSION:Zingerone enhances the inhibitory effects of nilotinib on CML cell survival and overcomes nilotinib resistance by suppressing the PI3K pathway.
Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker for oxidative DNA damage, is commonly used to assess the repair of reactive oxygen species (ROS) induced DNA damage. This study developed predictive models to quantify 8-OHdG concentrations in urine samples based on demographic and exposure-related variables from metal workers (21.27 ng/ml) and controls (12.63 ng/ml) using ELISA and machine learning algorithms. Three models; Random Forest Regressor (RFR), Support Vector Machine Regressor (SVMR), and Gradient Boosting Regressor (GBR) were evaluated for their predictive performance using metrics like Mean Squared Error (MSE), Root Mean Squared Error (RMSE), R-squared (R2), Mean Absolute Error (MAE), and classification metrics including Accuracy, Precision, Recall, and F1 Score. The RFR emerged as the best regression model with an MSE of 1.35, RMSE of 1.16, R2 of 0.92, and precision of 0.89 where feature importance analysis indicated exposure and age as key predictors. The SVMR showed slightly lower performance (MSE = 1.54, R2 = 0.91, precision = 0.83). GBR had reduced regression performance (MSE = 1.66, RMSE = 1.29, R2 = 0.90) but achieved superior classification metrics all at 0.89. Overall, RFR provided the most accurate predictions, while GBR excelled in balancing classification performance. These findings indicated the efficiency of machine learning in quantifying oxidative stress biomarkers.
Myocardial ischemia-reperfusion injury (MIRI) is the primary cause of death for acute myocardial infarction. LncRNA NNT-AS1 was upregulated in the H9c2 hypoxia-reoxygenation (H/R) model. However, the interaction between sevoflurane and NNT-AS1 is unknown in MIRI. The specific aim of this study was to explore the mechanism by which sevoflurane regulates cardiomyocyte injury via the NNT-AS1/miR-23a-3p/USP24 axis. The Caspase-3 level and apoptosis rate were used to assess the cell apoptosis level. Reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH), glutathione disulfide (GSSG), GSH/GSSG ratio, the total iron content, and Glutathione Peroxidase 4 (GPX4) protein content were measured to evaluate the level of ferroptosis. The targeting relationship was detected by the dual-luciferase reporter gene assay. In the H9c2 H/R model, the NNT-AS1 and USP24 levels were increased, but miR-23a-3p was decreased. The cell damage was aggravated, and apoptosis and ferroptosis were promoted. However, the NNT-AS1 and USP24 expression was downregulated, and miR-23a-3p expression was upregulated by sevoflurane pre-treatment. Cell damage, apoptosis, and ferroptosis were also improved. NNT-AS1 functions as a molecular sponge for miR-23a-3p. The NNT-AS1 overexpression further aggravated cell damage, apoptosis, and ferroptosis, while miR-23a-3p overexpression reversed the damaging effect of NNT-AS1. In summary, sevoflurane pretreatment alleviates apoptosis and ferroptosis in H/R-stimulated cardiomyocytes by regulating the NNT-AS1/miR-23a-3p/USP24 signaling axis, which may provide a potential target for MIRI treatment.
OBJECTIVE:This study aims to preliminarily investigate the regulatory role of the PI3K/Akt/NF-κB signaling pathway in the process of wasp venom-induced acute liver injury. METHODS:Rats were randomly divided into four groups using a random number table: Control group, PDTC group, ALI group, and ALI+PDTC group. RESULTS:Significant changes were observed in the ALI group in the following aspects: (1) Behavioral Changes: Rats exhibited reduced activity and agitation 6 h after toxin exposure, with gradual relief observed after 24 h. (2) Biochemical Tests: The ALT and AST levels were significantly elevated at all time points (p < 0.05). (3) Pathological Changes: Liver cord structure disorganization, extensive necrosis, and neutrophil infiltration were observed, indicating time-dependent liver injury. (4) Inflammatory Cytokines: Levels of IL-6, TNF-α, and IFN-γ were significantly increased (p < 0.05), while IL-10 levels were decreased (p < 0.05). (5) Protein Expression: The expression of PI3K, Akt, and NF-κB p65 proteins was significantly elevated (p < 0.05). No significant differences were found between the Control and PDTC groups (p > 0.05), while the ALI+PDTC group showed notable relief. CONCLUSION:This study successfully established a rat model of acute liver injury induced by wasp venom and found that the aberrant activation of the PI3K/Akt/NF-κB signaling pathway may contribute to liver injury progression by promoting inflammation. The NF-κB inhibitor PDTC significantly alleviated liver injury, an effect possibly associated with suppression of this pathway, providing a new theoretical basis for targeted treatment of secondary liver injury caused by clinical wasp stings.
