Toxicology Mechanisms and Methods最新文献

{"title":"Computational evidence of cancer and reproductive toxicological potential from short-chain PFAS exposure through network toxicology and docking approaches.","authors":"Vedika Jain, Sharda Bharti","doi":"10.1080/15376516.2025.2570331","DOIUrl":"https://doi.org/10.1080/15376516.2025.2570331","url":null,"abstract":"<p><p>Short-chain per- and polyfluoroalkyl substances (PFAS) are increasingly being used as substitutes for long-chain PFAS due to their lower bioaccumulation potential. However, their persistence and mobility can lead to toxicity and pose significant long-term health risks. Hence, the present study aims to investigate the toxicity and the molecular mechanisms associated with cancer and reproductive toxicity linked to short-chain PFAS based on network toxicology and molecular docking. The short-chain PFAS representatives used in this study include PFBA, PFBS, PFHxA, and PFHpA. The predicted biological targets for PFBA, PFBS, PFHxA, and PFHpA are 6, 2, 20, and 34, respectively. Potential targets from the disease library were identified and analyzed for protein-protein interactions and pathway enrichment. The top five targets were selected for molecular docking studies to examine interactions. Molecular docking indicated strong interactions between biological targets and pollutants, mainly through hydrogen bonds and salt bridges. Short-chain PFAS representatives have shown strong interaction with proteins such as HDAC3 (-6.133 kcal/mol), SHBG (-6.176 kcal/mol), PPARD (-6.355 kcal/mol and -6.205 kcal/mol), and FABP4 (-6.091 kcal/mol). This study also used molecular dynamics (MD) simulations to validate interactions, revealing significant dynamic behavior between proteins and ligands. Fourteen proteins linked to short-chain PFAS were associated with cancer and reproductive toxicity, with many targets common across diseases. Notably, PFHxA and PFHpA share several target proteins, suggesting similar effects in the body. Overall, the study provides an overview of the biological targets of short-chain PFAS and their potential health impacts.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-17"},"PeriodicalIF":2.7,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145337463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipidomic reveals potential mediators of associations between lead exposure and Alzheimer's disease.","authors":"Hong-Mei Gan, Cui-Ju Liu, Rong-Juan Jiang, Zhi-Yong Zhang, Bo Qian","doi":"10.1080/15376516.2025.2576266","DOIUrl":"https://doi.org/10.1080/15376516.2025.2576266","url":null,"abstract":"<p><p>Previous studies have identified associations between lead (Pb) exposure and the incidence of Alzheimer's disease (AD), yet the underlying mechanisms are still missing. This investigation verified the association between Pb exposure burden and AD risk in a small case-control study. Using a nontargeted quantification lipidomic assay, the role of 3034 lipid metabolites in the associations between Pb exposure and AD risk was also explored. The results showed that serum Pb levels in AD patients were significantly higher than in control individuals. Meanwhile, serum Pb levels were positively associated with an increased risk of AD (OR = 1.10, 95% CI = 1.04-1.15). Lipidomic assay identified that four lipid metabolites, including phosphatidylcholine (PC) (33:2e), diacylglycerol (DG) (19:1e), sphingomyelins (SM) (d38:4), and phosphoserine (PS) (39:1), were significantly altered in the serum of AD patients. Among them, PC(33:2e) and SM(d38:4) were positively correlated with serum Pb levels. Moreover, PC(33:2e) and SM(d38:4) demonstrated mediation contributions of 60.49% and 20.38%, respectively, in the association between Pb exposure and AD incidence. Network toxicology suggests that Pb exposure may affect lipid metabolic processes in AD by modulating the activation of the MAPK, PI3K-Akt, AMPK, mTOR, and autophagy pathways. Our findings reveal novel insights into AD pathogenesis, suggesting that lipid metabolites may play a mediating role in the association between Pb exposure burden and AD risk.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-14"},"PeriodicalIF":2.7,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145309383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondria under fire: toxicological mechanisms of brominated flame retardants.","authors":"Raul Ghiraldelli Miranda, Ivo F Machado, Anabela Pinto Rolo, Daniel Junqueira Dorta, Carlos M Palmeira","doi":"10.1080/15376516.2025.2568145","DOIUrl":"10.1080/15376516.2025.2568145","url":null,"abstract":"<p><p>Brominated flame retardants (BFRs) are ubiquitous and persistent environmental contaminants owing to their extensive use in consumer products. Although linked to various adverse health effects, the underlying molecular mechanisms remain complex. This review consolidates scientific evidence positioning mitochondria as a central target of BFR toxicity, unraveling the pathways that drive cellular damage. The analysis revealed that BFRs converge on the fundamental mechanisms of mitochondrial injury. They consistently impair bioenergetics by disrupting the electron transport chain and uncoupling oxidative phosphorylation, leading to ATP depletion and collapse of the mitochondrial membrane potential (ΔΨm). This energetic failure triggers a surge in reactive oxygen species, overwhelming antioxidant defenses, and causing severe oxidative damage. Beyond these common effects, this review highlights remarkable mechanistic plasticity. Tetrabromobisphenol A can induce distinct cell death programs, including apoptosis, necroptosis, and ferroptosis, depending on the cellular context of the study. Furthermore, BFR biotransformation can yield metabolites such as hydroxylated polybrominated diphenyl ethers (PBDEs) that exhibit significantly greater toxicity than their parent compounds. Finally, mitochondrial dysfunction is a central hub that orchestrates cellular damage by BFRs. This is critically highlighted by the replacement of BDE-209 with decabromodiphenyl ethane, a regrettable substitution, where the new compound shares similar mitotoxic mechanisms and has become a widespread pollutant. This underscores the urgent need for a paradigm shift toward mechanism-based risk assessment to prevent future cycles of hazardous chemical replacements and to guide the design of genuinely safer alternatives.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-28"},"PeriodicalIF":2.7,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145193117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"L-arginine and tetrahydrobiopterin alleviate mercury-induced vascular dysfunction by modulating angiotensin II receptors (AT1, AT2) and ACE2 activity in rat aortic rings.","authors":"Zana H Ibrahim, Ridha H Hussein, Ismail M Maulood","doi":"10.1080/15376516.2025.2567420","DOIUrl":"10.1080/15376516.2025.2567420","url":null,"abstract":"<p><strong>Background: </strong>Cardiovascular diseases are often driven by oxidative stress and endothelial dysfunction, particularly under heavy metal exposure such as HgCl₂. It disrupts NO signaling and RAS balance, impairing vascular function. L-arginine (LA) and tetrahydrobiopterin (BH₄) as essential regulators of eNOS, are potential therapeutic agents for restoring vascular reactivity.</p><p><strong>Objective: </strong>This study aimed to evaluate the protective effects of LA and BH₄, individually and in combination, on Ang II-induced vascular reactivity in isolated rat aortic rings under normal and HgCl₂-induced oxidative stress conditions. The interaction of Ang-II receptors (AT₁, AT₂) and ACE2 activity were explored.</p><p><strong>Methods: </strong>Aortic rings were pretreated with LA, BH₄, or both, followed by stimulation with Ang II (10^-11-10^-6 M). Pharmacological inhibitors were used to assess the roles of AT₁ (1 µM), AT₂ (10 µM), and ACE2 (1 µM) receptors. Vascular responsiveness was analyzed through Emax, pD₂, and AUC values in the presence and absence of HgCl₂ (1 µM).</p><p><strong>Results: </strong>HgCl₂ significantly impaired Ang II-induced vasoconstriction. LA and BH₄ partially restored vascular responsiveness, with the combination producing the most substantial improvements, indicating synergistic NO-mediated effects. AT₁ receptor blockade abolished Ang II responses, confirming its central role, while AT₂ inhibition increased contraction, revealing its vasodilatory function. ACE2 inhibition enhanced Ang II-induced contraction, particularly after HgCl₂ exposure. Co-treatment with LA and BH₄ mitigated this effect, restoring balance.</p><p><strong>Conclusion: </strong>LA and BH₄ can reverse HgCl₂-induced vascular dysfunction by enhancing NO signaling and modulating Ang II receptor pathways. Their combined use offers therapeutic promise in conditions involving oxidative stress and RAS dysregulation.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-16"},"PeriodicalIF":2.7,"publicationDate":"2025-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145193153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nano and microplastics: unveiling their profound impact on endocrine health.","authors":"Faezeh Jahedi, Neamatollah Jaafarzadeh Haghighi Frad, Mohammad Ali Khaksar, Parisa Rashidi, Farhad Safdari, Zahra Mansouri","doi":"10.1080/15376516.2025.2509745","DOIUrl":"10.1080/15376516.2025.2509745","url":null,"abstract":"<p><p>Plastics are extensively used materials with a long environmental lifespan, posing significant risks to human health and the environment. Global plastic consumption has surged, with plastic waste expected to triple by 2060. The primary concern is the breakdown of plastics into nano and micro-sized particles, which can enter the body and have been detected in various organs and tissues. This review systematically examines the effects of micro and nanoplastics (MNPs) on the endocrine system using <i>in vitro</i> and <i>in vivo</i> experimental models. Following PRISMA guidelines, articles were sourced from databases like PubMed, Web of Science, and Scopus. After screening for relevance and removing duplicates and non-English articles, 103 articles focusing on the endocrine effects of MNPs were selected. MNPs can disrupt endocrine functions, altering reproductive hormones and gene expression patterns. <i>In vivo</i> exposure to MNPs increases inflammatory markers such as TNF-α, IL-6, IL-1β, and NF-κB, leading to apoptosis, inflammation, and oxidative stress. These disruptions impact the gonads, thyroid glands, and hormone secretion from the pituitary and hypothalamus. Most studies focus on terrestrial animals, with polystyrene being the most commonly used polymer. Future research should explore various plastic polymers, longer exposure durations, a broader range of concentrations, and human-level studies to better understand the toxicity of plastic particles. Reducing exposure to these pollutants requires legal changes, consumer behavior adjustments, and increased public awareness. Understanding the underlying processes can help propose methods to mitigate risks and protect human health.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"865-893"},"PeriodicalIF":2.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144161145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation of some metal levels in people using electronic cigarettes and IQOS.","authors":"Yunus Yüce, Benay Can Eke","doi":"10.1080/15376516.2025.2506796","DOIUrl":"10.1080/15376516.2025.2506796","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;There has been a sharp increase in the use of e-cigarettes and heated tobacco products (HTPs) in the last decade. Related to the increase in the use, serious public health debates have been caused by the safety and risks of these products. Particularly due to the exposure to a lot of toxic substances, including heavy metals, there has been an increasing concern over their health effects. Heavy metals such as lead, arsenic, mercury, and cadmium are environmental pollutants poising significant health risks. These metals have a disposition to accumulate in the human body over time. Even at lower levels of exposure, they might lead to multiple organ damage and adverse health effects, including neurotoxicity, nephrotoxicity, and being carcinogenicity.&lt;/p&gt;&lt;p&gt;&lt;p&gt;This study tests the idea that using electronic cigarettes (e-cigarettes) and IQOS devices raises the levels of metals in urine and that the amount of increase depends on which product is used. The study aims to look at the levels of lead, cadmium, nickel, zinc, and selenium in the urine of cigarette smokers, e-cigarette users, IQOS users, and nonsmokers; to check for significant differences in metal levels between these groups (with a significance level set at &lt;i&gt;p&lt;/i&gt; &lt; 0.05); to compare the metal levels found with safety limits; and to explore if there's a link between the metal levels in urine and the type of product used (cigarettes, IQOS, or e-cigarettes).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Method: &lt;/strong&gt;This study aimed to compare the trace element, heavy element, and nicotine exposures of individuals who smoke (&lt;i&gt;n&lt;/i&gt; = 39), use e-cigarettes (&lt;i&gt;n&lt;/i&gt; = 28), use IQOS (&lt;i&gt;n&lt;/i&gt; = 20), and do not use tobacco or tobacco products (&lt;i&gt;n&lt;/i&gt; = 30) while living in Ankara, Türkiye. In order to evaluate the element levels of the participants, the levels of lead, cadmium, nickel, zinc, and selenium metals in their urine were determined using inductively coupled plasma mass spectrometry (ICP-MS), and nicotine exposures were determined using liquid chromatography-tandem mass spectrometry (LC-MS/MS).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The measurement showed that lead levels were higher in IQOS users (8.51 ng/g creatinine) and smokers (3.67 ng/g creatinine) compared to e-cigarette users (1.38 ng/g creatinine), and this difference was statistically significant (&lt;i&gt;p&lt;/i&gt; &lt; 0.05). In addition, a statistically significant difference was found between the cotinine level and lead level of the smoking and IQOS groups (&lt;i&gt;p&lt;/i&gt; ˂ 0.05). No statistically significant difference was found between the groups in terms of cadmium level (&lt;i&gt;p&lt;/i&gt; &gt; 0.008). Nickel level was found to be higher in e-cigarette (3.43 ng/g creatinine) and IQOS (3.84 ng/g creatinine) users than in the smoking group (0.99 ng/g creatinine). In terms of nickel, a statistically significant difference was found between the e-cigarette and IQOS groups and both the smoking and control groups (&lt;i&gt;p&lt;/i&gt; ˂ 0.05). No statistically signif","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1023-1038"},"PeriodicalIF":2.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144080495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of acute, subacute, subchronic, reproductive, and genotoxicity of a standardized extract from the bark of <i>Oroxylum indicum</i>.","authors":"Anju Majeed, Anjali Pandey, Chaitra Gurumallesha, Sarang Bani","doi":"10.1080/15376516.2025.2508755","DOIUrl":"10.1080/15376516.2025.2508755","url":null,"abstract":"<p><p><i>Oroxylum indicum</i> extract (OIE), prepared from its dried bark, known for neuroprotective and cognitive health support, is evaluated. <i>Oroxylum indicum,</i> the Indian Trumpet Tree, is traditionally known for its numerous medicinal benefits. Almost every part of the plant has been traditionally applied to treat many conditions such as stomachache, rheumatism, jaundice, cough, pharyngitis, acute and chronic bronchitis. Various researchers have demonstrated biological activities including antioxidant, and anti-inflammatory, immunomodulatory, analgesic, anti-cancer, anthelmintic, hepatoprotective, antiulcer, anti-diarrheal, cardioprotective, anti-diabetic, anti-epileptic, wound healing, properties. Since very little scientific evidence was available on safety assessment of OIE, a detailed toxicological evaluation of OIE was executed to ensure its safety for human administration and to harness its potential therapeutic applications. The present study evaluated the acute, subacute, subchronic, and reproductive toxicity of OIE in rodents. Also, the mutagenic potential was evaluated with the bacterial reverse mutation assay and the mammalian bone marrow micronucleus test.</p><p><p>No treatment-related study findings were observed, and a No Observed Adverse Effect Level of 400 mg/kg body weight was established in subacute, subchronic, reproductive/developmental toxicity studies. In addition, the findings of genotoxicity as evaluated by <i>in vitro</i> bacterial reverse mutation assay, and <i>in vivo</i> mammalian bone marrow micronucleus test in mice showed that OIE did not induce any mutagenic effects. Henceforth, this toxicological evaluation confirms that oral administration of OIE was found to be safe in rodents, non-mutagenic, without any adverse effects. This study positively impacts in encouraging the use of OIE in various therapeutic applications ensuring its safety.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1039-1056"},"PeriodicalIF":2.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical and forensic toxicology of bromism and bromoderma: mechanisms, diagnosis, and treatment.","authors":"Joana Coelho-Silva, Juliana Faria, Ricardo Jorge Dinis-Oliveira","doi":"10.1080/15376516.2025.2522220","DOIUrl":"10.1080/15376516.2025.2522220","url":null,"abstract":"<p><p>Bromism is a syndrome that results from bromide intoxication. It is difficult to diagnose since it mimics a myriad of psychiatric and dermatological disturbances. Historically, the most common sources have been drug ingestion or contaminated drinks. This work aims to thoroughly review all the state-of-the-art aspects of bromism and bromoderma, including its pathophysiology, diagnosis, treatment, and other relevant clinical and forensic features. In this context, a comprehensive search was conducted in PubMed (U.S. National Library of Medicine) without time restrictions. Bromism may occur in individuals of any age or gender, but it is more frequent in women. In children, it usually occurs under therapy for resistant epilepsy or is breastfed by mothers who ingested bromide and may manifest as bromoderma. In adults, bromism manifests with psychiatric and neurological signs such as hallucinations, delusions, or ataxia. Pseudohyperchloremia with a negative anion gap is highly suggestive of the diagnosis. Treatment requires the removal of bromide, which is achieved by <i>per os</i> or intravenous saline administration or even hemodialysis. Although bromism is not usually observed in clinical and forensic practice, it is still related to the administration of controlled or immediate-release formulations, mainly analgesics or antiepileptic drugs, as well as internet-purchased supplements.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"943-968"},"PeriodicalIF":2.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144326896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neodymium nitrate promotes the apoptosis of mouse liver cells via Bcl2l1/Caspase 3 pathway.","authors":"Jing Leng, Ning Wang, Xiu-Li Chang, Xiao-Peng Zhang, Jing Xu, Zheng-Li Yang, Ke-Lei Qian, Zhi-Qing Zheng, Gong-Hua Tao, Xu-Dong Jia, Ping Xiao, Xin-Yu Hong","doi":"10.1080/15376516.2025.2501253","DOIUrl":"10.1080/15376516.2025.2501253","url":null,"abstract":"<p><strong>Background: </strong>Neodymium, as a strategic rare earth element (REE), has demonstrated bioaccumulative potential and can permeate human systems through inhalation of airborne particulates, ingestion of contaminated food/water, and dermal absorption from soil matrices, ultimately eliciting multi-organ toxicological manifestations. However, the hepatotoxicological profile of neodymium species and their pathophysiological mechanisms remain inadequately characterized. Neodymium nitrate (Nd(NO₃)₃), the predominant water-soluble neodymium species, exhibits marked bioavailability with particular hepatic tropism.</p><p><strong>Objective: </strong>This study aims to investigate the effects of neodymium nitrate on apoptosis of mouse liver cells and its underlying molecular mechanisms.</p><p><strong>Results: </strong>Mouse liver cell line AML12 was treated with gradient concentrations of neodymium nitrate. The results showed that neodymium nitrate inhibited liver cell proliferation, induced apoptosis, and exhibited a dose-dependent relationship. Western blotting and quantitative real-time PCR (qRT-PCR) revealed that neodymium nitrate suppressed Bcl2l1 transcription and activated the proteolysis of Caspase 3. To further explore the molecular mechanism, Bcl2l1 protein was overexpressed in mouse liver cells. The findings indicated that overexpression of Bcl2l1 rescued neodymium nitrate-induced apoptotic phenotypes and attenuated Caspase 3 cleavage.</p><p><strong>Conclusion: </strong>The present data suggest that neodymium nitrate induces apoptosis of mouse liver cells through the Bcl2l1/Caspase 3 pathway. However, further studies are called for to substantiate this view, as the findings may provide critical mechanistic evidence for revising the toxicological risk assessment frameworks of rare earth elements.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"993-1002"},"PeriodicalIF":2.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144000390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The possible mechanisms of trans fatty acid effects on digestive disorders based on computational toxicology: a case study of elaidic acid.","authors":"Chenyang Yu, Fule Wang, Xinfang Zhang, Changchuan Bai, Guanhua Lv","doi":"10.1080/15376516.2025.2503873","DOIUrl":"10.1080/15376516.2025.2503873","url":null,"abstract":"<p><p>Trans fatty acids (TFAs) are potential health risk factors generated during food processing, and their mechanisms of association with digestive diseases remain incompletely elucidated. This study focused on elaidic acid (EA), integrating computational toxicology and molecular docking to systematically analyze its molecular mechanisms in regulating functional dyspepsia (FD), gastric cancer (GC), nonalcoholic fatty liver disease (NAFLD), and colorectal cancer (CRC) through multi-target networks. Protein Interaction Networks were constructed by screening EA and disease-intersecting targets, enriching and analyzing key pathways, and validating the binding ability of core targets. Results showed that EA shared 22, 67, 56, and 72 common targets with FD, GC, NAFLD, and CRC, respectively. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses indicated that EA acts through pathways including lipid metabolism dysregulation, inflammatory response, and chemical carcinogenesis-receptor activation. Molecular docking confirmed binding affinities between EA and core targets. The present study suggests that EA may promote the progression of digestive diseases through a multi-target-multi-pathway model, providing a new perspective for the study of the toxicity mechanism of TFA and food safety prevention and control.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1011-1022"},"PeriodicalIF":2.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144049980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}