Toxicology Research最新文献_第5页

Exploring the role of key gene PTTG1 in clear cell renal carcinoma based on bioinformatics analysis and In-vitro cell experiments. 基于生物信息学分析和体外细胞实验探讨关键基因PTTG1在透明细胞肾癌中的作用。

IF 2.2 4区医学

Toxicology Research Pub Date : 2025-06-17 eCollection Date: 2025-06-01 DOI: 10.1093/toxres/tfaf078

Li-Hui Guan, Yu-Dong Wu

{"title":"Exploring the role of key gene PTTG1 in clear cell renal carcinoma based on bioinformatics analysis and In-vitro cell experiments.","authors":"Li-Hui Guan, Yu-Dong Wu","doi":"10.1093/toxres/tfaf078","DOIUrl":"10.1093/toxres/tfaf078","url":null,"abstract":"This study aimed at exploring the expression characteristics and functional roles of PTTG1 in ccRCC by bioinformatics analysis and in-vitro experiments. Differentially expressed genes were screened based on TCGA-KIRC and GSE168845 and the protein-protein interaction network was constructed. The risk regression model was constructed by Lasso regression and the key prognostic genes were obtained by combining immune infiltration and pathway enrichment analysis. Genes and proteins were quantified using RT-qPCR and western blot. MTT assay was used to detect the vitality of cells. Cell apoptosis and cell cycle were detected by flow cytometry. The comet assay was adopted to detect the damage degree of cell DNA. Six significant DDR-relevant prognostic genes (CCNA2, CDC45, CTLA4, FOXM1, PLK1, and PTTG1) were obtained. Immune infiltration results showed that CTLA4 was significantly positively correlated to T cells CD8. Besides, PTTG1 was negatively correlated to T cells CD4 memory resting, but remarkably positively correlated with both T cells CD8 and T cells regulatory. Compared with normal renal proximal tubular epithelial cells, the protein expression of PTTG1 was up-regulated at both mRNA and protein levels in ccRCC tissues. PTTG1could notably promote the proliferation of 786-O cells, and significantly inhibited apoptosis, cycle arrest and DNA damage of 786-O cells. PTTG1 may play a carcinogenic role by promoting the proliferation of ccRCC cells and inhibiting apoptosis. PTTG1 is expected to become a potential diagnostic and prognostic biomarker as well as an immunotherapy target for ccRCC.","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 3","pages":"tfaf078"},"PeriodicalIF":2.2,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12203000/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144525568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The ameliorative effects of metformin and taurine against thioacetamide hepatotoxicity in rats. 二甲双胍和牛磺酸对大鼠硫乙酰胺肝毒性的改善作用。

IF 2.2 4区医学

Toxicology Research Pub Date : 2025-06-09 eCollection Date: 2025-06-01 DOI: 10.1093/toxres/tfaf076

Sherouk S Badawy, Mohammad M Mashaly, A F Abdel-Aziz, Mai M Madkour

{"title":"The ameliorative effects of metformin and taurine against thioacetamide hepatotoxicity in rats.","authors":"Sherouk S Badawy, Mohammad M Mashaly, A F Abdel-Aziz, Mai M Madkour","doi":"10.1093/toxres/tfaf076","DOIUrl":"10.1093/toxres/tfaf076","url":null,"abstract":"The main objective of this research was to investigate the therapeutic, anti-inflammatory, and histological effects of metformin and taurine, both alone and in combination, against thioacetamide (TAA)-induced hepatotoxicity in rats. The study included forty adult male Swiss albino rats, which were divided into five groups: Group I provided the control group. Group II (TAA group) rats received injections of TAA (200 mg/kg b.wt /3 times/week, i.p.) for six weeks. Group III (TAA + metformin) rats received administration of metformin (200 mg/kg/day, p.o.) for five weeks. Group IV (TAA + taurine) rats received injections of taurine (100 mg/kg/day, i.p.) for five weeks, while Group V (TAA + metformin + taurine) rats received daily intraperitoneal injections and oral administration of the medication for five weeks. Inflammation and changes in liver function are hallmarks of TAA-induced hepatotoxicity. Our findings demonstrated that the greatly improved liver dysfunction might be attributed to the effects of metformin and taurine. Furthermore, a combination of metformin and taurine markedly inhibited inflammatory responses, as indicated by the decreased levels of the inflammatory cytokine IL-6. The biochemical results were confirmed by the histological analyses of the liver tissues. Post-treatments of metformin and taurine might have crucial potential and synergistic effects against TAA-induced hepatotoxicity.","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 3","pages":"tfaf076"},"PeriodicalIF":2.2,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12146511/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144264905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Hepatoprotective mechanisms of ginkgo-Biloba and dandelion extracts: antioxidant activity and modulation of TNF-α and P53 pathways in Thioacetamide-induced liver injury. 银杏叶和蒲公英提取物的肝保护机制：硫代乙酰胺诱导肝损伤的抗氧化活性和TNF-α和P53通路的调节。

IF 2.2 4区医学

Toxicology Research Pub Date : 2025-06-08 eCollection Date: 2025-06-01 DOI: 10.1093/toxres/tfaf075

Heba M Shaaban, El-Sayed E Mehana, Samah S Oda, Hossam G Tohamy, Dina R Gad El-Karim, Mustafa Shukry

{"title":"Hepatoprotective mechanisms of ginkgo-Biloba and dandelion extracts: antioxidant activity and modulation of TNF-α and P53 pathways in Thioacetamide-induced liver injury.","authors":"Heba M Shaaban, El-Sayed E Mehana, Samah S Oda, Hossam G Tohamy, Dina R Gad El-Karim, Mustafa Shukry","doi":"10.1093/toxres/tfaf075","DOIUrl":"10.1093/toxres/tfaf075","url":null,"abstract":"Liver injuries, especially those induced by chemical toxins and pharmaceuticals, are increasingly prevalent. This study evaluated the hepatoprotective effects of Ginkgo biloba and dandelion extracts in a rat model of thioacetamide (TAA)-induced liver injury. Twenty-eight male albino rats were randomly assigned to four groups: control, TAA-treated, TAA plus G. biloba (100 mg/kg), and TAA plus dandelion (500 mg/kg). TAA administration over eight weeks significantly elevated serum liver enzymes (AST, ALT, ALP, and GGT), bilirubin, cholesterol, and triglycerides (P < 0.05) while significantly reducing total protein and albumin levels (P < 0.05). TAA also induced oxidative stress, evident by increased hepatic malondialdehyde and reduced glutathione levels (P < 0.05). Co-treatment with G. biloba or dandelion extracts significantly ameliorated these biochemical alterations (P < 0.05), with G. biloba demonstrating slightly stronger effects. Histopathological examination showed reduced necrosis, fibrosis, and inflammatory cell infiltration in treated groups. Immunohistochemical analysis confirmed decreased expression of TNF-α and P53 proteins (P < 0.05), indicating anti-inflammatory and anti-apoptotic properties. These findings suggest that G. biloba and dandelion extracts confer protective effects against TAA-induced liver damage through antioxidant, anti-inflammatory, and anti-apoptotic mechanisms.","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 3","pages":"tfaf075"},"PeriodicalIF":2.2,"publicationDate":"2025-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12145877/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144256870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Use of new approach methodology for hepatic safety assessment of covalent inhibitor drug candidates. 应用新方法评价共价抑制剂候选药物的肝脏安全性。

IF 2.2 4区医学

Toxicology Research Pub Date : 2025-05-25 eCollection Date: 2025-06-01 DOI: 10.1093/toxres/tfaf054

Sara Amberntsson, Alison J Foster, Bhavik Chouhan, Stephen Wilkinson, Stephanie Harlfinger, Graham Smith, Jason G Kettle, Michael Niedbala, Stefan Kavanagh, Dominic P Williams

{"title":"Use of new approach methodology for hepatic safety assessment of covalent inhibitor drug candidates.","authors":"Sara Amberntsson, Alison J Foster, Bhavik Chouhan, Stephen Wilkinson, Stephanie Harlfinger, Graham Smith, Jason G Kettle, Michael Niedbala, Stefan Kavanagh, Dominic P Williams","doi":"10.1093/toxres/tfaf054","DOIUrl":"10.1093/toxres/tfaf054","url":null,"abstract":"Interest in inhibiting target proteins through covalent binding mechanisms has increased in the last decade due to the potential for beneficial pharmacological properties. However, the inherent targeted covalent inhibitor (TCI) adverse off-target reactivity risk requires a mitigation strategy early during drug discovery. The aim of this research was to design a pre-clinical hepatic safety assessment strategy for TCIs considering risk associated with electrophilic warhead reactivity and reactive metabolites formation at clinically-relevant plasma concentrations. The mitigation strategy was applied to compound 35, a potent irreversible inhibitor to KRASG12C. Drug induced liver injury was assessed in primary human hepatocyte spheroids. GSH and ATP depletion were investigated for compound 35 and 6 other marketed TCIs containing an acrylamide warhead which binds irreversibly to cysteine-containing target proteins. None of the TCIs showed GSH depletion prior to ATP depletion after 7-days exposure, suggesting that GSH depletion was not driving cytotoxicity in the spheroids. The calculated hepatotoxicity margin towards plasma exposure of 2.5 for compound 35 was found to be in the same range as for the two KRASG12Cinhibitors adagrasib and sotorasib, with clinically reported treatment-related adverse aminotransferase elevations leading to dose modifications. The safety evaluation reported here suggests no negative discrepancy in liver toxicity for compound 35 versus similar approved TCI's. Finally, the risk associated with detected oxidative metabolites was further mitigated as the pan-CYP450 inhibitor 1-aminobenzotriazole (ABT) had no effect on the cytotoxicity response following incubation of compound 35 in the presence and absence of ABT.","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 3","pages":"tfaf054"},"PeriodicalIF":2.2,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12103896/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144148844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Protective effects of apricot kernel oil and metformin against BPA-induced ovarian toxicity in rat models of polycystic ovary syndrome: insights into PI3K/AKT and mitochondrial apoptosis pathways. 杏仁油和二甲双胍对bpa诱导的多囊卵巢综合征大鼠卵巢毒性的保护作用：对PI3K/AKT和线粒体凋亡途径的见解

IF 2.2 4区医学

Toxicology Research Pub Date : 2025-05-25 eCollection Date: 2025-06-01 DOI: 10.1093/toxres/tfaf071

Xuejuan Jiao, Qianqian Zhang, Guoliu Ye, Fang Xing, Dongmei Xie, Liqun Wang

{"title":"Protective effects of apricot kernel oil and metformin against BPA-induced ovarian toxicity in rat models of polycystic ovary syndrome: insights into PI3K/AKT and mitochondrial apoptosis pathways.","authors":"Xuejuan Jiao, Qianqian Zhang, Guoliu Ye, Fang Xing, Dongmei Xie, Liqun Wang","doi":"10.1093/toxres/tfaf071","DOIUrl":"10.1093/toxres/tfaf071","url":null,"abstract":"In this study, the therapeutic synergistic effects of metformin (MET) and Apricot Kernel Oil (AKO) were investigated in an animal model of bisphenol A (BPA)-induced polycystic ovary syndrome (PCOS). BPA disrupts endocrine functions and induces oxidative stress in ovarian tissues, leading to PCOS. AKO and MET target underlying mechanisms associated with PCOS, particularly those related to insulin resistance and oxidative stress, which are critical in the pathology of this condition. Antioxidant activities, total phenolic, and flavonoid contents of AKO were performed. The AKO underwent liquid chromatographic-electrospray ionization tandem mass-spectrometric (LC-ESI-MS/MS) analysis after acetonitrile treatment. PCOS was induced in adult Wistar rats by administering BPA. After 60 days, the 70 rats were divided into seven groups (n = 10/group): Normal, PCOS, MET, AKO, and co-treatment with MET and AKO. On the 22ndday of the study, serum catalase, glutathione peroxidase, superoxide dismutase activity, LH, FSH, progesterone, estrogen, and testosterone hormones alongside inflammatory cytokines (TNF-a, IL-6, CRP, and IL-1β) and nitric oxide levels were measured. Ovarian tissues were isolated for measurements of ferric reducing ability of plasma and thiobarbituric acid reactive substances levels. The expression of genes and proteins related to mitochondrial and PI3K/AKT pathways was analyzed. The results demonstrated that AKO, in synergy with MET, modulated hormone levels, reduced pro-inflammatory cytokines, and enhanced antioxidant properties. AKO, in combination with MET modulated apoptosis via mitochondrial and PI3K/AKT pathways. These findings suggest that AKO holds promise as a potential therapeutic option for women with ovulation disorders, particularly those affected by bisphenol A-induced PCOS.","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 3","pages":"tfaf071"},"PeriodicalIF":2.2,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12103898/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144148753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Structural insights and predictive modelling of a novel anti-HER2 scFv and Leptulipin: a newly designed immunotoxin protein for HER2 positive cancers. 一种新型抗HER2 scFv和Leptulipin的结构见解和预测模型：一种新设计的用于HER2阳性癌症的免疫毒素蛋白。

IF 2.2 4区医学

Toxicology Research Pub Date : 2025-05-24 eCollection Date: 2025-06-01 DOI: 10.1093/toxres/tfaf060

Maria Kalsoom, Hafiz Muzzammel Rehman, Yasamin Al-Qassab, Hafiz Muhammad Rehman, Rabbani Syed, Nadeem Ahmed, Yurong Wu, Ahmed A Al-Qahtani, Tariq Nadeem, Hamid Bashir

{"title":"Structural insights and predictive modelling of a novel anti-HER2 scFv and Leptulipin: a newly designed immunotoxin protein for HER2 positive cancers.","authors":"Maria Kalsoom, Hafiz Muzzammel Rehman, Yasamin Al-Qassab, Hafiz Muhammad Rehman, Rabbani Syed, Nadeem Ahmed, Yurong Wu, Ahmed A Al-Qahtani, Tariq Nadeem, Hamid Bashir","doi":"10.1093/toxres/tfaf060","DOIUrl":"10.1093/toxres/tfaf060","url":null,"abstract":"Targeted therapy is one crucial therapeutic approach frequently employed in cancer treatment. In almost 30% of human breast cancers, a transmembrane tyrosine kinase receptor named the HER2 (human epidermal growth factor receptor 2) is overexpressed, establishing HER-2 as a promising target for cancer treatment. The goal of the current work is to computationally design and analyze a new chimeric protein that could selectively target HER2-positive breast cancer cells based on a single polypeptide chain variable fragment and leptulipin (an anticancer peptide) fusion. After the computational joining of the secondary structure, 3D modeling, quality validation, physicochemical properties, docking, interaction analysis, MD simulation, and energy calculations were performed using various computational tools and online servers. The most precise predicted chimeric protein model was docked to the HER-2 receptor using ClusPro 2.0, which revealed a significant number of hydrogen bonds and salt bridges reflecting the fusion protein's quality, validity, interaction, and stability. These results were further supported by MD simulation on the Desmond Schrodinger module, which predicted a stable docked complex. This was also evident by principal component analysis and the negative energy value of MM/PBSA. These comprehensive in silico analyses, coupled with a high predicted expression value of 0.94 in E. coli by the SOLUPROT, collectively highlight the potential of fusion protein as a potent therapeutic agent against breast cancer and open a potential avenue for targeted cancer therapy and provide a groundwork for in vitro and in vivo validation that might lead to clinical implication.","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 3","pages":"tfaf060"},"PeriodicalIF":2.2,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12102063/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

PGC-1 alpha regulates mitochondrial biogenesis to promote silica-induced pulmonary fibrosis. PGC-1 α调节线粒体生物发生，促进二氧化硅诱导的肺纤维化。

IF 2.2 4区医学

Toxicology Research Pub Date : 2025-05-23 eCollection Date: 2025-06-01 DOI: 10.1093/toxres/tfaf070

Xiaoqiang Han, Mei Zhang, Liu Daowei, Lulu Liu, Xin Ma, Yu Xiong, Huifang Yang, Zhihong Liu, Na Zhang

{"title":"PGC-1 alpha regulates mitochondrial biogenesis to promote silica-induced pulmonary fibrosis.","authors":"Xiaoqiang Han, Mei Zhang, Liu Daowei, Lulu Liu, Xin Ma, Yu Xiong, Huifang Yang, Zhihong Liu, Na Zhang","doi":"10.1093/toxres/tfaf070","DOIUrl":"10.1093/toxres/tfaf070","url":null,"abstract":"Silicosis is an incurable chronic fibrotic lung disease caused by long-term exposure to respirable silica particles. It is characterized by persistent inflammation and progressive fibrosis of lung tissues, which eventually leads to respiratory failure and seriously affects human health. The high incidence and mortality associated with silicosis have made the disease a widespread public health concern. However, its pathogenesis has not been fully elucidated. Mitochondrial biogenesis plays a crucial role under various fibrotic conditions. However, the mechanism of this process in silicosis is still unclear. Therefore, this study aimed to explore the influence of the PGC-1α gene on mitochondrial biogenesis in the development of silicosis. We established in vivo and in vitro silicosis models by exposing rats and rat type-2 alveolar epithelial cells (RLE-6TN) to silica. Our findings revealed alterations in the mitochondrial structure and function, decreased mitochondrial biogenesis, and reduced expression of mtDNA (Mitochondrial DNA) content. By upregulating the PGC-1α gene in RLE-6TN cells, we activated the PGC-1α- NRF1-TFAM signaling pathway, enhancing mitochondrial biogenesis, increasing citrate synthase and mtDNA content, improving mitochondrial function, and mitigating fibrosis. Our results indicate that the regulation of mitochondrial biogenesis can affect silicosis-induced fibrosis, highlighting the significance of reduced mitochondrial biogenesis in the progression of silicosis-induced fibrosis.","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 3","pages":"tfaf070"},"PeriodicalIF":2.2,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12100742/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Intratracheal instillation of graphene oxide with different diameters suppressed toll-like receptor 3-mediated lipid droplet biogenesis in lungs and livers of mice. 气管内灌注不同直径的氧化石墨烯可抑制小鼠肺和肝脏中toll样受体3介导的脂滴生物生成。

IF 2.2 4区医学

Toxicology Research Pub Date : 2025-05-17 eCollection Date: 2025-06-01 DOI: 10.1093/toxres/tfaf069

Yijin Wang, Xiaomin Tang, Sihuan Luo, Zhaohui Zhang, Yi Cao

{"title":"Intratracheal instillation of graphene oxide with different diameters suppressed toll-like receptor 3-mediated lipid droplet biogenesis in lungs and livers of mice.","authors":"Yijin Wang, Xiaomin Tang, Sihuan Luo, Zhaohui Zhang, Yi Cao","doi":"10.1093/toxres/tfaf069","DOIUrl":"10.1093/toxres/tfaf069","url":null,"abstract":"Recent advances have established lipid droplets as dynamic innate immune hubs coordinating cellular metabolism and defense mechanisms. While previous studies primarily focused on nanomaterials (NMs) altering lipid metabolism to influence lipid droplet dynamics, this study pioneers the investigation of NM-induced immune modulation via Toll-like receptor (TLR) pathways as a novel regulatory axis for lipid droplets. Building on our prior findings that graphene oxide (GO) impaired TLR3-mediated lipid signaling, we systematically explored the role of GO's diameter in modulating this process. Mice were subjected to daily intratracheal instillation of three GO variants (50-200 nm, <500 nm or > 500 nm) at 1 mg/kg for 7 days. Although no significant change in body weight or organ coefficient was observed, all GO exposure suppressed lipid staining in mouse lungs and livers, correlating with altered co-localization of TLR3 and perilipin 2 (PLIN2), critical regulators of lipid droplet biogenesis. Down-regulation of TLR3 signaling components, namely interferon induced protein with tetratricopeptide repeats 1 (IFIT1), radical S-adenosyl methionine domain containing 2 (RSAD2), and PLIN2, occurred in a diameter-dependent manner, with GO 50-200 nm showing the most pronounced effects, likely attributable to the smallest hydrodynamic size and polydispersity index in suspension. This work provides evidence that NM geometry governs TLR-mediated lipid droplet regulation, bridging the knowledge gap between nanotoxicology and immunometabolic cross-talking, a paradigm distinct from conventional lipid metabolism-focused nanotoxicological studies.","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 3","pages":"tfaf069"},"PeriodicalIF":2.2,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12085196/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Impacts of Ficus Religiosa-loaded chitosan nanoparticles against indomethacin induced peptic ulcer in rats: promising therapy with enhanced bioavailability and gastro-protective activity. 载无花果壳聚糖纳米颗粒对吲哚美辛诱导的大鼠消化性溃疡的影响：具有增强生物利用度和胃保护活性的有希望的治疗方法。

IF 2.2 4区医学

Toxicology Research Pub Date : 2025-05-15 eCollection Date: 2025-06-01 DOI: 10.1093/toxres/tfaf034

Sumaira Anjum, Mohamed Mohamed Soliman, Fayez Althobaiti, Shatha B Albattal, Momina Riaz Dar, Mubashara Inam, Amna Komal Khan, Ahmed Elshehawi, Huma Mujahid

{"title":"Impacts of Ficus Religiosa-loaded chitosan nanoparticles against indomethacin induced peptic ulcer in rats: promising therapy with enhanced bioavailability and gastro-protective activity.","authors":"Sumaira Anjum, Mohamed Mohamed Soliman, Fayez Althobaiti, Shatha B Albattal, Momina Riaz Dar, Mubashara Inam, Amna Komal Khan, Ahmed Elshehawi, Huma Mujahid","doi":"10.1093/toxres/tfaf034","DOIUrl":"10.1093/toxres/tfaf034","url":null,"abstract":"Peptic ulcer is a chronic inflammatory disorder affecting large portion of population with difficulty in treatment. Treatment options include inhibition of gastric acid secretion, histamine inhibitors, eradication of Helicobacter pylori infection and tissue lining protection. These therapeutic options have several side effects, low bioavailability and bio-distribution. To further increase bioavailability, control release, stability, site specific delivery and minimize organoleptic side effects of phytochemical, nano-encapsulation is a suitable strategy. Chitosan is a suitable nano-carrier for drug delivery applications in treating peptic ulcer as it is biodegradable, biocompatible, safe and cost-effective. Therefore, Ficus religiosa (FR) leaf extract was loaded into chitosan NPs by ion gelation method for in vivo anti-ulcerative activity in indomethacin-induced peptic ulcer rats. Results showed that FR extract was successfully loaded into CNPs with 84% encapsulation efficiency while the size of empty CNPs was reported to be 620.3 nm as compared to FR-loaded CNPs 811.5 nm. FR-loaded CNPs showed homogeneous size distribution as well greater physical stability. Furthermore, in vivo studies revealed gastro-protective activity of FR-loaded CNPs in reducing the ulcer index (UI) to 0.51 (71.30% inhibition) while indomethacin only untreated rats showed UI 2.99 and insignificant ulcer inhibition 11.02%. Furthermore, FR-loaded CNPs restored gastric pH, healed rat stomach completely without ulcers or hemorrhagic spot and improved antioxidants and blood profiles compared to plant extract or CNPs. These findings confirmed the effective application of FR extract loaded CNPs as anti-ulcer agents and reinforces the importance of nano-encapsulation in improving drug efficacy.","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 3","pages":"tfaf034"},"PeriodicalIF":2.2,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078930/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

LncRNA MALAT1 serves as a risk factor in perioperative respiratory adverse events in children under general anesthesia. LncRNA MALAT1是全麻患儿围手术期呼吸不良事件的危险因素。

IF 2.2 4区医学

Toxicology Research Pub Date : 2025-05-13 eCollection Date: 2025-06-01 DOI: 10.1093/toxres/tfaf068

Yuan Gao, Bo Wang, Shuai Wang, Yanyan Jiang, Dalong Wang, Quan Lin, Ke Liu, Shuai Zhang, Ying Cheng, Jimei Xu

{"title":"LncRNA MALAT1 serves as a risk factor in perioperative respiratory adverse events in children under general anesthesia.","authors":"Yuan Gao, Bo Wang, Shuai Wang, Yanyan Jiang, Dalong Wang, Quan Lin, Ke Liu, Shuai Zhang, Ying Cheng, Jimei Xu","doi":"10.1093/toxres/tfaf068","DOIUrl":"10.1093/toxres/tfaf068","url":null,"abstract":"The perioperative respiratory adverse events (PRAE) are ineluctable during pediatric anesthesia. Accurate assessment of preoperative anesthesia is significant to reduce surgical risks in general anesthesia. This study focused on the expression level and predictive performance of lncRNA MALAT1 in PRAE for general anesthesia children. 236 medical records from children patients were included and they were divided into the No-PRAE group (n = 129) and the PRAE group (n = 107). Blood samples obtained before general anesthesia were used to evaluate the relative levels of MALAT1 by qRT-PCR. The multivariate logistic regression analysis was carried out to identify underlying risk factors. The receiver operator characteristic (ROC) curve was plotted to estimate the diagnostic performance of MALAT1 in the occurrence of PRAE. The serum MALAT1 in the PRAE group was identified to be higher than that in the No-PRAE group. The regression analysis indicated that patients with preoperative airway disease (OR: 2.813; 95%CI: 1.327-5.961) or longer anesthesia duration (OR: 2.131; 95%CI: 1.111-4.088) or higher levels of MALAT1 (OR: 13.019; 95%CI: 6.769-25.039) faced a higher risk of PRAE. The area under the ROC curve was 0.885 while the sensitivity and specificity were 79.44% and 82.17%, respectively, identifying the referrible value of MALAT1 as a risk factor for predicting PRAE in general anesthesia children. In conclusion, the increased MALAT1 was a potential indicator of predicting PRAE in general anesthesia children.","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 3","pages":"tfaf068"},"PeriodicalIF":2.2,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12074572/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144075185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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