Journal of Biochemical and Molecular Toxicology最新文献

{"title":"Toxic Effects of Extracellular Histones on Neuronal Cells: Mitochondrial Dysfunction and Apoptosis","authors":"Wei Cao,&nbsp;Jun Fang","doi":"10.1002/jbt.70477","DOIUrl":"10.1002/jbt.70477","url":null,"abstract":"<div>\u0000 \u0000 <p>Extracellular histones, emerging as critical inflammatory mediators, have unclear yet significant implications in nerve injury. This study, through in vitro assays using PC-12 and SH-SY5Y neuronal cells, reveals the toxicological mechanisms of histones. Histones trigger calcium influx and disrupt mitochondrial function by opening the MPTP, resulting in a marked decline in MMP. This mitochondrial perturbation further leads to Cyt-C release and upregulation of Caspase-3, triggering apoptotic cell death. However, interventions with MgSO4 and CsA mitigate histone-induced toxicity by blocking calcium influx and inhibiting MPTP opening. These results enhance our understanding of histone-related neurotoxicity and may contribute to developing antidotes against histone-mediated nerve damage at the biochemical and molecular toxicology levels.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Camphene Mitigates Cyclophosphamide-Induced Oxidative Stress, Neuroinflammation, and Cognitive Dysfunction via Nrf2, NF-κB, and Astrocytic GFAP Modulation in Wistar Albino Rats","authors":"Mohd Almas Khan,&nbsp;Mohammad Mumtaz Alam,&nbsp;Syed Mansoor Ali,&nbsp;Syed Ehtaishamul Haque","doi":"10.1002/jbt.70514","DOIUrl":"https://doi.org/10.1002/jbt.70514","url":null,"abstract":"<div>\u0000 \u0000 <p>Cyclophosphamide (CP) is a potent chemotherapeutic medication for various cancer types. Chemotherapy-associated neurotoxicity is a significant adverse effect seen in cancer patients undergoing treatment with cyclophosphamide. The root cause of this toxicity is the production of reactive oxygen species (ROS). Camphene (CAMP) is a natural substance that has demonstrated its effectiveness as a potent antioxidant and anti-inflammatory molecule. Hence, we have selected Camphene to evaluate its potential role in mitigating CP-induced neurotoxicity in rats. CAMP was administered orally at 50, 100, and 200 mg/kg doses from Day 1 to Day 21. On Day 7, the rats were administered with CP at 200 mg/kg via intraperitoneal injection. Neurobehavioral assessments including elevated plus maze test (EPM), forced swim test (FST), grip strength test (GST), and sucrose preference test (SPT) were performed. On Day 21, the rats were euthanized, and their brains were extracted for examining histopathological, Immunohistochemical, Oxidative stress and Anti-inflammatory parameters. Nuclear Factor kappa B (NF-κB), Nuclear Factor Erythroid 2–related Factor 2 (Nrf2), Glial Fibrillary Acidic Protein (GFAP), Superoxide Dismutase (SOD), Catalase (CAT), Glutathione Reductase (GR), Thiobarbituric Acid Reactive Substances (TBARS), Interleukin-6 (IL-6), Interleukin-1β (IL-1β), Interleukin-10 (IL-10), and Tumour Necrosis Factor-alpha (TNF-α) were assessed. Camphene at 100 and 200 mg/kg exhibited neuroprotective effects and prevented neurological disorders induced by cyclophosphamide (CP) at 200 mg/kg by reversing oxidative stress, inflammation, and neurobehavioral changes. Camphene, thus, exhibited dose-dependent neuroprotection by increasing antioxidant level, decreasing neuroinflammation, and enhancing behavioural outcomes.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145062446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Mitigated Effect of the Combination of Metformin and Stearic Acid to Ameliorate Bleomycin-Induced Pulmonary Fibrosis in Rats via Inhibiting Gal-3/Smad3/α-SMA and TNF-α/NF-κβ Signaling Pathways","authors":"Maha M. Salem,&nbsp;Nermin S. Youssef,&nbsp;Mai El Keiy,&nbsp;Abeer A. Khamis","doi":"10.1002/jbt.70494","DOIUrl":"https://doi.org/10.1002/jbt.70494","url":null,"abstract":"<div>\u0000 \u0000 <p>Pulmonary fibrosis (PF) is a chronic, inflammatory interstitial lung disease. It is promoted by overproliferation of fibroblasts characterized by the progressive formation of scar tissue in the lung parenchyma, which leads to an inexorable decline in lung function, respiratory failure, and high mortality. This study aims to assess the synergetic consequences of metformin and stearic acid, whether individually or in combination, to ameliorate bleomycin-induced PF in rat models via suppressing Gal-3/Smad3/α-SMA and TNF-α/NF-κβ signaling pathways and mitigate its adverse side effect on kidneys and liver. The antioxidant/oxidative stress shuttle system was estimated in lung, liver, and kidney tissues. Moreover, histopathology assessment and immunohistochemical staining for NF-κβ antibodies were performed in the lung and trachea tissues. Additionally, RT-qPCR gene expressions of TNF-α, IL-1β, IL-6, and α-SMA were investigated. The expression levels of Gal-3, <i>p</i>-Gal-3, Smad3, and <i>p</i>-Smad3 protein in lung tissues were determined by western blot analysis. The findings showed that metformin and/or stearic acid exhibited antifibrotic and anti-inflammatory impacts in-vivo as evidenced by enhanced body weight, liver and kidney functions, reduced oxidative stress, increased endogenous antioxidant enzymes, downregulated inflammatory cytokine levels IL-1β, IL-6, and TNF-α, and attenuation effect on α-SMA, a major marker of myofibroblasts. Furthermore, there was a marked improvement in the profibrotic Gal-3/Smad3 signaling pathway. On the other hand, a significant reduction in the histological score of fibrosis and immunohistochemical expression NF-κβ levels was detected, especially in the combination-treated group. Overall, our findings elucidate the synergetic antifibrotic impact of metformin and stearic acid which could be used as a potential candidate drug against various chronic inflammatory diseases.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145062799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Kynurenine 3-hydroxylase Inhibitor RO 61-8048 Alleviates Nonalcoholic Fatty Liver Disease in High-Fat Diet-Induced Obese Mice","authors":"Yang Liu,&nbsp;Huaiyu Xing,&nbsp;Tong Zhou,&nbsp;Cuiting Hao,&nbsp;Shuang Wang,&nbsp;Jiguang Liu","doi":"10.1002/jbt.70511","DOIUrl":"https://doi.org/10.1002/jbt.70511","url":null,"abstract":"<div>\u0000 \u0000 <p>Nonalcoholic fatty liver disease (NAFLD) caused by childhood obesity has become an important public health problem, leading to hepatic fat accumulation, inflammation, hepatocyte apoptosis, and potential liver dysfunction. Kynurenine monooxygenase (KMO) is an enzyme of the kynurenine (Kyn) pathway, which is associated with various chronic diseases. Here, we investigated the effect of KMO inhibitor (RO 61-8048) via the kynurenine pathway for the treatment of NAFLD. In this study, C57BL/6 mice were fed with high-fat diet (HFD) and fructose/sucrose (55%:45%) for to simulate fatty degeneration in vivo. Hepatic lipid peroxidation, steatosis, inflammasome activation and apoptosis were examined. In vitro, AML12 cells was incubated with free fatty acids (FFAs) for 24 h to study the potential mechanism of RO 61-8048 treatment. Histopathological examination indicated that RO 61-8048 alleviated hepatic steatosis, lipid vacuolization, and inflammatory cell infiltration in HFD-fed mice. RO 61-8048 significantly reduced the body weights and liver weights, and ameliorated serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), High-density lipoprotein cholesterol (HDL-C), Low density lipoprotein cholesterol (LDL-C) and produce quinolinic acid (QUIN) levels in C57BL/6 mice. Compared to HFD-fed mice, RO 61-8048 alleviated release of inflammatory cytokines (tumor necrosis factor-α (TNF-α), interleukin (IL)−1β, IL-6) and hepatic apoptosis. A dual luciferase reporter assay suggested the interaction between SP3 and KMO promoter. Consistent with the in <i>vivo</i> results, RO 61-8048 alleviated lipid droplet accumulation and reduced lipid reactive oxygen species (ROS) levels and apoptosis in AML12 cells. Collectively, our study demonstrates that transcription factor specificity protein 3 (SP3) is able to bind with the promoter of KMO. The KMO inhibitor (RO 61-8048) ameliorates lipid metabolism, inflammatory injury and hepatocyte apoptosis in NAFLD through the tryptophan-kynurenine pathway, potentially serving as a promising candidate for alleviating NAFLD.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145062443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lycorine Exerts Antitumor Effects on the Osimertinib-Resistant Non-Small Cell Lung Cancer by Inhibiting NOTCH3/HES1 Signaling","authors":"Chen Wang,&nbsp;Chaoyang Zeng,&nbsp;Aimin Wang,&nbsp;Yue Shang,&nbsp;Jun Ni,&nbsp;Gaojie Li,&nbsp;Liping Li,&nbsp;Shuohan Xi,&nbsp;Wendie Wang,&nbsp;Shuzhen Chen","doi":"10.1002/jbt.70501","DOIUrl":"https://doi.org/10.1002/jbt.70501","url":null,"abstract":"<div>\u0000 \u0000 <p>The resistance of non-small cell lung cancer (NSCLC) to osimertinib unavoidably occurs in clinical use. Lycorine is isolated from <i>Amaryllidaceae genera</i> and possesses a variety of pharmacological effects including anticancer. Here, we investigated the influences of lycorine on osimertinib-resistant cells and its underlying mechanisms. The data from CCK8 assay, wound healing, and migration assay revealed the inhibitory effect of lycorine in the NSCLC cells resistant to osimertinib. In vivo, lycorine reduced the growth of osimertinib-resistant NSCLC xenografts. The results from transcriptomic analysis showed that lycorine significantly decreased the level of Notch3 mRNA in osimertinib-resistant PC9 (PC9/OR) cells. It was verified that lycorine indeed lowered the level of Notch3 mRNA/protein and its downstream Hes1 protein in osimertinib-resistant cells. The MMP9 and MMP2 protein levels were also lessened in the resistant cells after lycorine treatment. Moreover, Notch3/Hes1 protein levels were higher in osimertinib-resistant cells than those in osimertinib-sensitive cells. Notch3 and Hes1 knockdown promoted the antiproliferation and anti-migration effects of osimertinib in the resistant cells. Notably, lycorine enhanced the antitumor activity of osimertinib against its resistant cells both in vitro and in vivo. Overall, our data reveal that lycorine inhibits the proliferation and metastasis of osimertinib-resistant NSCLC cells via Notch3/Hes1 pathway.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145062432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Effect of Sulfasalazine on Renal Damage in Sepsis Model Induced by Cecal Ligation and Puncture in Rats","authors":"Zeynep Çiçek,&nbsp;Murat Çakır,&nbsp;Ali Aydın,&nbsp;Burak Bircan,&nbsp;Semanur Fırat,&nbsp;Suat Tekin","doi":"10.1002/jbt.70513","DOIUrl":"https://doi.org/10.1002/jbt.70513","url":null,"abstract":"<div>\u0000 \u0000 <p>Sepsis is a medical condition that occurs when a harmful inflammatory response damages tissues and organs. The kidneys are among the organs most frequently affected by sepsis. Anti-inflammatory strategies are crucial in treating sepsis. The anti-inflammatory properties of sulphasalazine (SFZ) have been demonstrated in various in vitro and in vivo studies. This study investigates the effect of SFZ on kidney damage in a rat model of sepsis induced by the cecal ligation and puncture (CLP) method. Animals were divided into control, CLP, CLP + SFZ50, and CLP + SFZ250. Two doses of SFZ (50 and 250 mg/kg) were applied in two different treatment groups after CLP. The administration of SFZ reduced the CLP-induced increase in serum blood urea nitrogen (BUN), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), kidney injury molecule-1 (KIM-1), and creatinine (Cre) levels for both doses (<i>p</i> &lt; 0.05). Additionally, SFZ treatment significantly decreased histopathological damage, phosphorylated NF-κB, toll-like receptor-4 (TLR-4), IL-1β, phosphorylated IκB-α, interleukin-6 (IL-6), TNF-α, caspase-3, and caspase-8 levels (<i>p</i> &lt; 0.05). In this study, we found that two different doses of SFZ (50 and 250 mg/kg) showed protective effects by decreasing inflammation and kidney damage in a CLP-induced experimental sepsis model.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145062434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LncRNA ROR1-AS1 Stimulates Epithelial-Mesenchymal Transition and Chemoresistance of Pancreatic Cancer by Upregulating HMGB1 Through miR-33a-5p Adsorption","authors":"RenZhe Tang,&nbsp;XiaoQing You","doi":"10.1002/jbt.70499","DOIUrl":"https://doi.org/10.1002/jbt.70499","url":null,"abstract":"<div>\u0000 \u0000 <p>The work aimed at exploring the potential mechanism of Long noncoding RNA tyrosine protein kinase transmembrane receptor 1 antisense RNA 1 (ROR1-AS1) in the process of epithelial-mesenchymal transition (EMT) of pancreatic cancer (PC) cells resistant to Gemcitabine (GEM). ROR1-AS1 expression was analyzed in PC tissues, cells, PANC-1/GEM-resistant cell lines, and its correlation with PC clinicopathological features was determined. The proliferation ability, invasive and migratory properties of PC cells were evaluated, and the apoptotic rate was measured. EMT process of E-cadherin, N-cadherin, and Snail were analyzed. The direct molecular interactions within the ROR1-AS1/miR-33a-5p/HMGB1 axis were confirmed using dual-luciferase reporter and RNA immunoprecipitation assays. ROR1-AS1 expression was elevated in PC tissues, cells, and PANC-1/GEM cells. The survival rate of patients with higher ROR1-AS1 levels was lower, and expression was correlated with tumor node metastasis stage and lymph node metastasis. Silencing ROR1-AS1 supressed cell growth and EMT process, whilst overexpressing ROR1-AS1 was the opposite. ROR1-AS1 could bind miR-33a-5p to target and regulate HMGB1 and affect the biological behaviors of cancer cells. The suppressive influence of ROR1-AS1 knockdown was rescued when miR-33a-5p was silenced, meanwhile, the promoting influence of ROR1-AS1 overexpression was mitigated by silencing HMGB1. Cells resistant to GEM became more sensitive to GEM when miR-33a-5p was overexpressed or ROR1-AS1 was silenced, whereas the improvement of GEM resistance was offset by inhibiting miR-33a-5p or upregulating HMGB1. ROR1-AS1 modulates the growth and EMT process of PC through the miR-33a-5p/HMGB1 axis. ROR1-AS1 knockdown or miR-33a-5p overexpression is effective to reduce GEM resistance in PC.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145062513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Madecassoside Improves Renal Injury via Activation of AMPK/Autophagy in Experimental Membranous Nephropathy","authors":"Hongyan Liu,&nbsp;Yamei Ge,&nbsp;Zheng Wang,&nbsp;Hongyun Wang,&nbsp;Qiong Wang,&nbsp;Jun Yuan","doi":"10.1002/jbt.70509","DOIUrl":"https://doi.org/10.1002/jbt.70509","url":null,"abstract":"<div>\u0000 \u0000 <p>Currently, membranous nephropathy (MN) has received considerable attention in Chine due to its increasing prevalence and limited therapeutic approaches. Madecassoside (MA) is a natural compound with anti-inflammatory, antioxidant, anticancer, and wound healing effects. In this study, we aimed to investigate the roles and related mechanisms of MA in MN. The passive Heymann nephritis (PHN) model was established in rats to mimic human MN. MA was intraperitoneally injected into MN rats beginning 1 week after modeling for 4 weeks. Urine, blood samples, and kidney samples were collected for biochemical analysis and histopathological analysis. Western blot analysis and immunofluorescence staining were performed. MA relieved MN-induced renal dysfunctions and histopathology in rats. Additionally, MA reduced IgG and C3 deposition and alleviated podocyte injury in MN rats. Moreover, MA activated canonical autophagy by modulating AMPK/mTOR. Furthermore, MA ameliorated oxidative stress and inflammation in renal tissues of MN model rats. In conclusion, treatment with MA ameliorates proteinuria and renal dysfunctions in MN rats by activating AMPK/mTOR-mediated autophagy.</p>\u0000 </div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145062445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New methyl/benzyl-1,2,4-triazole-3-one Derivatives: Synthesis, Characterization (IR, NMR), Antidiabetic, Anti-Alzheimer, and Molecular Docking Study","authors":"Fatih Çelik,&nbsp;Yasemin Ünver,&nbsp;Halil İbrahim Güler,&nbsp;Ercan Oğuz,&nbsp;Fikret Türkan","doi":"10.1002/jbt.70510","DOIUrl":"https://doi.org/10.1002/jbt.70510","url":null,"abstract":"<div>\u0000 \u0000 <p>New 1,2,4-triazole compounds were synthesized in this study. These compounds (2,3,5,6 (a–f)) were characterized by IR, ¹H-NMR, and ¹³C-NMR studies. Acarbose was used as a standard for alpha glycosidase and alpha amylase enzymes, while tacrine molecule was used as a standard for acetylcholinesterase enzyme. While the IC₅₀ result of acarbose was found to be 6.430 ± 0.736, the IC₅₀ values for α-gly and α-amly enzymes were 1.454 ± 0.087 µM–3.7973 ± 0.3352 µM and 1.509 ± 0.161 µM–3.797 ± 0.335 µM, respectively. In addition, the IC₅₀ values for AChE enzyme were found to be in the range of 1.330 ± 0.118 µM–11.104 ± 3.463 µM. Except for molecules 5a, 5b and 5 f, all other molecules were found to be more active than the standard. Molecular docking simulations were conducted to explore the interactions of 3e and 3 f compounds with Human Acetylcholinesterase, using tacrine as a reference molecule, to evaluate binding affinities and key ligand-protein interactions.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145062444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Prognostic Significance of Vesicle-Mediated Transport-Related Genes as Risk Markers in Gastric Cancer","authors":"Yunjie Wan,&nbsp;Ganshu Xia,&nbsp;Shoumiao Li,&nbsp;Wei Zhang,&nbsp;Yanxin Gong,&nbsp;Xiaolong Liang,&nbsp;Zhiqiang Liu,&nbsp;Baozhong Li","doi":"10.1002/jbt.70508","DOIUrl":"https://doi.org/10.1002/jbt.70508","url":null,"abstract":"<div>\u0000 \u0000 <p>Vesicle-mediated transport plays a role in intercellular communication in tumor microenvironment, affecting tumor development and prognosis. This study attempted to establish risk markers for gastric cancer (GC) based on vesicle-mediated transport-related genes, providing a new perspective for evaluating immunotherapeutic response and prognosis in GC patients. We used TCGA-STAD data set for training set and performed differential analysis and Cox regression analysis to establish a vesicle-mediated transport-related GC prognostic risk model to predict survival rate of GC patients. GC prognostic model was verified through TCGA-STAD and GSE84426 datasets. ROC curve presented that GC prognostic model had reliable prediction results, and the Kaplan-Meier survival curve presented that high-risk (HR) GC patients had unfavorable prognoses. The Cox regression analysis results reported that GC prognostic model had independent predictive ability for prognosis. Clinical feature analysis revealed that the majority of HR group patients were male and under 60 years old, with a high degree of malignancy. Using GC prognostic risk scores and clinical factors, we constructed a nomogram. Calibration, ROC, and DCA curves presented that nomogram had excellent predictive ability for patient prognosis. Immune infiltration analysis showed that HR GC patients had a lower overall proportion of immune cell infiltration and poorer immune function. Prediction of immunotherapeutic response showed that low-risk (LR) GC patients may be prone to benefit from immunotherapy. In conclusion, GC prognostic risk model had potential to forecast prognosis and immunotherapeutic efficacy of GC patients.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145062514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}