Omar Elshaarawy, Shuai Lan, Johannes Mueller, Sebastian Mueller
{"title":"Critical flicker frequency improves after alcohol detoxification and is associated with liver stiffness.","authors":"Omar Elshaarawy, Shuai Lan, Johannes Mueller, Sebastian Mueller","doi":"10.3748/wjg.v31.i36.107703","DOIUrl":"10.3748/wjg.v31.i36.107703","url":null,"abstract":"<p><strong>Background: </strong>Critical flicker frequency (CFF) is a quantitative tool for assessing hepatic encephalopathy (HE), particularly minimal HE, which is associated with poor prognosis in liver cirrhosis. Alcohol-related liver disease (ALD) is a leading global cause of cirrhosis; however, the effects of alcohol on CFF and its relationship with liver stiffness (LS) remain underexplored.</p><p><strong>Aim: </strong>To study the impact of alcohol withdrawal on CFF and its correlation with LS in ALD patients.</p><p><strong>Methods: </strong>A total of 108 patients were included: 93 heavy drinkers hospitalized for detoxification, 15 with non-ALD etiologies, and 20 healthy controls. CFF was measured using the Hepatonorm analyzer, and LS <i>via</i> transient elastography (FibroScan). Baseline and post-detoxification assessments were conducted in 57 ALD patients.</p><p><strong>Results: </strong>The cohort had a mean age of 53.7 ± 13.8 years, with 74% male participants. CFF measurements were reliable, with 97.2% of patients showing an interquartile range < 20%. ALD patients exhibited significantly lower CFF compared to controls. Receiver operating characteristic analysis for overt HE (<i>n</i> = 12) yielded an area under the curve of 0.66 (95% confidence interval: 0.49-0.84, <i>P</i> = 0.0142), with an optimal cutoff of 36.5 Hz. CFF significantly improved post-detoxification. Patients with LS > 17 kPa had lower CFF, while those with intermediate LS showed no significant difference.</p><p><strong>Conclusion: </strong>CFF is influenced by HE severity and acute alcohol exposure, showing improvement after detoxification. Its weak correlation with fibrosis stage suggests that CFF serves as a sensitive neurocognitive marker in ALD.</p>","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":"31 36","pages":"107703"},"PeriodicalIF":5.4,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12476681/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145193347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Colonic neoplasia and celiac disease: A systematic review.","authors":"Yasir M Khayyat","doi":"10.3748/wjg.v31.i36.110210","DOIUrl":"10.3748/wjg.v31.i36.110210","url":null,"abstract":"<p><strong>Background: </strong>Celiac disease (CD) is a chronic inflammatory disease that affects multiple systems in genetically predisposed individuals. The only known treatment for CD is adherence to a gluten-free diet. Gluten has been found to exert deleterious immune-inflammatory effects beyond the small bowel, involving several genetic, cellular, and paracellular mechanisms in the context of chronic inflammation, leading to colorectal carcinoma (CRC) in CD patients. Several neoplasms, including adenocarcinoma and lymphoma, are associated with CD. Despite strong evidence of an association between CD and small intestinal malignancies, CRC is less common and underdiagnosed in patients with CD. In practice, most CD patients are only monitored for small bowel complications despite mild lower gastrointestinal symptoms; thus, colonoscopy is underused, with a greater focus on upper endoscopy and small bowel biopsy, a major hindrance in early diagnosis. Delayed diagnosis and poor prognosis have also been linked to nonspecific symptoms and late presentations. The lack of screening guidelines appears to be a critical gap due to disconnection between CD and heterogeneous expression of the disease complications add further diagnostic delay.</p><p><strong>Aim: </strong>To critically evaluate and synthesize existing evidence on the association between CD and CRC to encourage early-stage detection through lower gastrointestinal screening in CD patients and suggest individual-specific management strategies.</p><p><strong>Methods: </strong>The Scopus, Web of Science, and PubMed databases were searched <i>via</i> Medical Subject Headings words related to the criteria pertinent to CD and colon cancer/neoplasm, with a focus on pathophysiological mechanisms, clinical presentations, and outcomes reviewed.</p><p><strong>Results: </strong>A total of 3028 citations related to CD and neoplasia were initially identified. Following a critical review and exclusions, 136 citations were suitable for inclusion in this study. Despite its low incidence, a clinically significant association was found between CRC and CD that could impact the overall patient survival rate, suggesting early screening investigations, individual-specific interventions, and further longitudinal studies.</p><p><strong>Conclusion: </strong>A low incidence of colon lymphoma and adenocarcinoma has been revealed. The clinical presentation of colon lymphoma and adenocarcinoma is indolent and nonspecific, with late presentation in the form of adhesions and perforation. A modest but statistically significant increase in CRC risk among CD patients was noted. Several overlapping factors, including individual variability, genetic and environmental factors, diagnostic delays and duration of gluten exposure, compliance with a gluten-free diet, lack of educational awareness, and complex immune-inflammatory interactions, were found to contribute to the overall incidence of CRC in CD patients. However, the true i","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":"31 36","pages":"110210"},"PeriodicalIF":5.4,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12476670/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145193354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Application of deep learning-based convolutional neural networks in gastrointestinal disease endoscopic examination.","authors":"Yang-Yang Wang, Bin Liu, Ji-Han Wang","doi":"10.3748/wjg.v31.i36.111137","DOIUrl":"10.3748/wjg.v31.i36.111137","url":null,"abstract":"<p><p>Gastrointestinal (GI) diseases, including gastric and colorectal cancers, significantly impact global health, necessitating accurate and efficient diagnostic methods. Endoscopic examination is the primary diagnostic tool; however, its accuracy is limited by operator dependency and interobserver variability. Advancements in deep learning, particularly convolutional neural networks (CNNs), show great potential for enhancing GI disease detection and classification. This review explores the application of CNNs in endoscopic imaging, focusing on polyp and tumor detection, disease classification, endoscopic ultrasound, and capsule endoscopy analysis. We discuss the performance of CNN models with traditional diagnostic methods, highlighting their advantages in accuracy and real-time decision support. Despite promising results, challenges remain, including data availability, model interpretability, and clinical integration. Future directions include improving model generalization, enhancing explainability, and conducting large-scale clinical trials. With continued advancements, CNN-powered artificial intelligence systems could revolutionize GI endoscopy by enhancing early disease detection, reducing diagnostic errors, and improving patient outcomes.</p>","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":"31 36","pages":"111137"},"PeriodicalIF":5.4,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12476647/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145193359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Minjee Kim, Yuwon Kim, Ji Eun Kim, Sung Noh Hong, Dong Kyung Chang, Young-Ho Kim, Eun Ran Kim
{"title":"Long-term outcomes of endoscopic resection of 1-1.5 cm sized grade 1 rectal neuroendocrine tumor: A retrospective study.","authors":"Minjee Kim, Yuwon Kim, Ji Eun Kim, Sung Noh Hong, Dong Kyung Chang, Young-Ho Kim, Eun Ran Kim","doi":"10.3748/wjg.v31.i36.109846","DOIUrl":"10.3748/wjg.v31.i36.109846","url":null,"abstract":"<p><strong>Background: </strong>Rectal neuroendocrine tumors (NETs) smaller than 10 mm and well-differentiated tumors are generally considered to have a low risk of lymph node and distant metastasis, making them suitable for endoscopic resection. In contrast, tumors ≥ 20 mm in size typically require surgical resection. However, the optimal management of intermediate-sized (10-15 mm) rectal NETs remains controversial.</p><p><strong>Aim: </strong>To compare the clinical outcomes of endoscopic resection of rectal NETs < 1 cm and those 1-1.5 cm in size.</p><p><strong>Methods: </strong>A retrospective study was conducted on 1056 patients with rectal NETs treated at the Samsung Medical Center between January 2005 and June 2021. After propensity score matching (1:10) for age, sex, and type of endoscopic resection, 225 patients with tumors < 1 cm in size and 27 patients with tumors 1-1.5 cm in size were analyzed.</p><p><strong>Results: </strong>Surgical resection was more frequent in the 1-1.5 cm group (37.2%) than in the < 1 cm group (10.7%) (<i>P</i> < 0.01). Endoscopic submucosal dissection was also more commonly performed in the 1-1.5 cm group (48.1% <i>vs</i> 18.5%, <i>P</i> < 0.01). Negative resection margins were achieved in 97.2% of the patients, with no significant difference between the groups (<i>P</i> = 0.22). No lymphovascular invasion was observed. During a median follow-up of 54 months, no recurrence occurred in the 1-1.5 cm group, while one case of metachronous recurrence was noted in the < 1 cm group (<i>P</i> = 1.00). There was no significant difference in recurrence-free survival (<i>P</i> = 0.48).</p><p><strong>Conclusion: </strong>Endoscopic resection of 1-1.5 cm grade 1 rectal NETs yielded comparable outcomes to those < 1 cm in size, suggesting its feasibility as a treatment.</p>","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":"31 36","pages":"109846"},"PeriodicalIF":5.4,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12476668/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145192893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Machine learning fibrosis score for pediatric metabolic dysfunction-associated steatotic liver disease: Promising but premature.","authors":"Toshifumi Yodoshi","doi":"10.3748/wjg.v31.i36.112217","DOIUrl":"10.3748/wjg.v31.i36.112217","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatotic liver disease (MASLD) is now the leading cause of chronic liver disease in children, affecting up to 38% with obesity of children. With the global shift from non-alcoholic fatty liver disease (NAFLD) to MASLD using affirmative criteria (hepatic steatosis plus ≥ 1 cardiometabolic risk factor) and approximately 99% concordance in pediatrics, the development of non-invasive fibrosis tools is accelerating. Yao <i>et al</i> report a machine-learning \"chronic MASLD with fibrosis (CH-MASLD-Fib)\" score for advanced fibrosis with area under the receiver operating characteristic curve (AUROC) of 0.92. While timely, we urge caution. First, high accuracy from a single-center cohort signals overfitting: Complex models can learn cohort-specific noise and fail to generalize. Consistent with this, established pediatric scores (NAFLD fibrosis score, fibrosis-4, pediatric NAFLD fibrosis score) perform modestly (AUROC: Approximately 0.6-0.7), and aspartate aminotransferase-to-platelet ratio index is variable, raising concern that CH-MASLD-Fib's result reflects a statistical artifact. Second, MASLD epidemiology varies by ethnicity (highest in Hispanic, lower in Black children); a model derived in a mono-ethnic Chinese cohort may misclassify other populations. Third, clinical utility and cost-effectiveness are unproven; dependence on specialized assays (<i>e.g.</i>, bile acids, cholinesterase) would limit access and increase cost. We recommend external validation in multi-ethnic cohorts, head-to-head comparisons with simple serum indices and elastography, and formal economic analyses. Until then, clinical judgment anchored in readily available markers and judicious, targeted liver biopsy remains paramount.</p>","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":"31 36","pages":"112217"},"PeriodicalIF":5.4,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12476683/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145192979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Identification of risk factors for <i>Clostridium difficile</i> infection in older adult hospitalized patients with pressure ulcers.","authors":"Qin Jiang, Dong-Xin Liu, Wei Lu, Hong-Fei Sang, Xiao-Mei Gong, Yu-Lei Li","doi":"10.3748/wjg.v31.i36.110355","DOIUrl":"10.3748/wjg.v31.i36.110355","url":null,"abstract":"<p><strong>Background: </strong><i>Clostridium difficile (C. difficile)</i> infection (CDI) is a common healthcare-associated infection. Older adult hospitalized patients with pressure ulcers are more susceptible because of low immunity and disordered flora, but their specific risk factors are unknown. This study hypothesizes that the use of antibiotics for more than 2 weeks, the use of proton pump inhibitors (PPIs), and the use of β-lactam antibiotics are independent risk factors for CDI in this population.</p><p><strong>Aim: </strong>To determine the risk factors for CDI in hospitalized older adults with pressure ulcers.</p><p><strong>Methods: </strong>A total of 120 older adults hospitalized with pressure ulcers from 2020 to 2023 were enrolled in the wound repair ward of the hospital. Stool samples were collected for anaerobic culture, <i>C. difficile</i> glutamate dehydrogenase (GDH) antigen and toxin detection, and multivariate logistic regression was used to analyze risk factors.</p><p><strong>Results: </strong>Among 120 older adults hospitalized patients with pressure ulcers, 39 tested positive for <i>C. difficile</i>, with an incidence rate of 32.5%. Thirty-nine patients (32.5%) were positive for GDH antigen. Twelve patients (10.0%) were positive for toxin A/B. Multivariate analysis shows that the use of antibiotics for more than 2 weeks, the use of proton pump inhibitors, and the use of β-lactam antibiotics are independent risk factors for CDI (all <i>P</i> values < 0.05).</p><p><strong>Conclusion: </strong>From 2020 to 2023, the incidence of CDI in 120 hospitalized older adult patients with pressure ulcers was 32.5%, and three independent risk factors were identified.</p>","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":"31 36","pages":"110355"},"PeriodicalIF":5.4,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12476682/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145193300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Predicting pathological complete response to chemoradiotherapy using artificial intelligence-based magnetic resonance imaging radiomics in esophageal squamous cell carcinoma.","authors":"Atsushi Hirata, Koichi Hayano, Toru Tochigi, Yoshihiro Kurata, Tadashi Shiraishi, Nobufumi Sekino, Akira Nakano, Yasunori Matsumoto, Takeshi Toyozumi, Masaya Uesato, Gaku Ohira","doi":"10.3748/wjg.v31.i36.111293","DOIUrl":"10.3748/wjg.v31.i36.111293","url":null,"abstract":"<p><strong>Background: </strong>Advanced esophageal squamous cell carcinoma (ESCC) has an extremely poor prognosis. Preoperative chemoradiotherapy (CRT) can significantly prolong survival, especially in those who achieve pathological complete response (pCR). However, the pretherapeutic prediction of pCR remains challenging.</p><p><strong>Aim: </strong>To predict pCR and survival in ESCC patients undergoing CRT using an artificial intelligence (AI)-based diffusion-weighted magnetic resonance imaging (DWI-MRI) radiomics model.</p><p><strong>Methods: </strong>We retrospectively analyzed 70 patients with ESCC who underwent curative surgery following CRT. For each patient, pre-treatment tumors were semi-automatically segmented in three dimensions from DWI-MRI images (<i>b</i> = 0, 1000 second/mm²), and a total of 76 radiomics features were extracted from each segmented tumor. Using these features as explanatory variables and pCR as the objective variable, machine learning models for predicting pCR were developed using AutoGluon, an automated machine learning library, and validated by stratified double cross-validation.</p><p><strong>Results: </strong>pCR was achieved in 15 patients (21.4%). Apparent diffusion coefficient skewness demonstrated the highest predictive performance [area under the curve (AUC) = 0.77]. Gray-level co-occurrence matrix (GLCM) entropy (<i>b</i> = 1000 second/mm²) was an independent prognostic factor for relapse-free survival (RFS) (hazard ratio = 0.32, <i>P</i> = 0.009). In Kaplan-Meier analysis, patients with high GLCM entropy showed significantly better RFS (<i>P</i> < 0.001, log-rank). The best-performing machine learning model achieved an AUC of 0.85. The predicted pCR-positive group showed significantly better RFS than the predicted pCR-negative group (<i>P</i> = 0.007, log-rank).</p><p><strong>Conclusion: </strong>AI-based radiomics analysis of DWI-MRI images in ESCC has the potential to accurately predict the effect of CRT before treatment and contribute to constructing optimal treatment strategies.</p>","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":"31 36","pages":"111293"},"PeriodicalIF":5.4,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12476672/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145192927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Correction to: Cytokeratin 8 is increased in hepatitis C virus cells and its ectopic expression induces apoptosis of SMMC7721 cells.","authors":"Ming-Zhu Sun, Shuang-Suo Dang","doi":"10.3748/wjg.v31.i36.112156","DOIUrl":"10.3748/wjg.v31.i36.112156","url":null,"abstract":"<p><p>[This corrects the article on p. 6178 in vol. 19, PMID: 24115814.].</p>","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":"31 36","pages":"112156"},"PeriodicalIF":5.4,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12476633/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145193362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Andrei Nicolae Ceobanu, Alexandru Florin Braniște, Ştefan Morărașu, Gabriel Mihail Dimofte
{"title":"From bench to bedside: Advancements in patient-derived xenografts for predicting therapy outcomes in colorectal cancer.","authors":"Andrei Nicolae Ceobanu, Alexandru Florin Braniște, Ştefan Morărașu, Gabriel Mihail Dimofte","doi":"10.3748/wjg.v31.i35.110370","DOIUrl":"10.3748/wjg.v31.i35.110370","url":null,"abstract":"<p><p>Colorectal cancer is the third most diagnosed malignancy and the second-leading cause of cancer-related deaths worldwide. Management includes a combination of surgery, radiotherapy, and systemic therapy that is tailored to the stage of the disease. However, each tumor has a unique genetic profile that influences the treatment response and the overall prognosis. Biomarkers guide treatment decisions, but many chemotherapeutics lack reliable predictors. To bridge this gap patient-derived xenograft models were developed and are valuable preclinical tools. These systems utilize patient-derived tumor tissue grafted into an animal host that provides a platform for personalized drug profiling. This article surveyed recent advances in mouse and zebrafish colorectal cancer patient-derived xenografts, emphasizing their clinical utility for functional precision oncology. We explored the impact of these models on translational research, discussed current limitations, and outlined key priorities for future development.</p>","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":"31 35","pages":"110370"},"PeriodicalIF":5.4,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12476665/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145193287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Reem S Alruhaimi, Emad H M Hassanein, Sulaiman M Alnasser, Ahmad F Ahmeda, Hanan S Althagafy, Omnia A M Abd El-Ghafar, Ayman M Mahmoud
{"title":"Ambroxol mitigates cyclophosphamide-induced liver injury by suppressing TLR-4/NF-κB signaling and oxidative stress and upregulating cytoglobin, TXNRD1 and HMGB1.","authors":"Reem S Alruhaimi, Emad H M Hassanein, Sulaiman M Alnasser, Ahmad F Ahmeda, Hanan S Althagafy, Omnia A M Abd El-Ghafar, Ayman M Mahmoud","doi":"10.3748/wjg.v31.i35.108139","DOIUrl":"10.3748/wjg.v31.i35.108139","url":null,"abstract":"<p><strong>Background: </strong>Cyclophosphamide (CP) is a potent chemotherapeutic and immunosuppressant agent, but its hepatotoxicity remains a significant concern. Ambroxol (ABX) is a mucolytic agent with emerging beneficial effects against oxidative stress and inflammation.</p><p><strong>Aim: </strong>To investigate the hepatoprotective effects of ABX against CP-induced liver injury, focusing on oxidative stress, inflammation, and the possible role of cytoglobin, thioredoxin reductase 1 (TXNRD1) and high-mobility group box 1 (HMGB1).</p><p><strong>Methods: </strong>ABX (20 mg/kg) was orally administered for 7 days, and the rats received a single injection of CP (100 mg/kg) on day 5. Blood and liver samples were collected for analyses, and the affinity of ABX towards cytoglobin, TXNRD1, and HMGB1 was evaluated using molecular docking.</p><p><strong>Results: </strong>CP administration significantly elevated alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase, reduced albumin, and caused multiple histopathological alterations in the liver. ABX effectively restored liver function biomarkers and attenuated histopathological alterations. CP-induced oxidative stress was evidenced by increased malondialdehyde and decreased glutathione and antioxidant enzyme activities, all of which were ameliorated by ABX. CP upregulated toll-like receptor 4 (TLR-4), nuclear factor-kappaB (NF-κB) p65 and pro-inflammatory cytokines, while downregulating cytoglobin, TXNRD1 and HMGB1. ABX suppressed TLR-4/NF-κB signaling and pro-inflammatory cytokines, and upregulated cytoglobin, TXNRD1 and HMGB1. <i>In silico</i> molecular docking revealed the affinity of ABX to bind with cytoglobin, TXNRD1, and HMGB1.</p><p><strong>Conclusion: </strong>ABX protects against CP hepatotoxicity by mitigating oxidative stress, suppressing TLR-4/NF-κB signaling, and upregulating cytoglobin, TXNRD1 and HMGB1. ABX showed binding affinity towards cytoglobin, TXNRD1 and HMGB1. These findings suggest that ABX has therapeutic potential in alleviating hepatotoxicity associated with CP treatment.</p>","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":"31 35","pages":"108139"},"PeriodicalIF":5.4,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12476691/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145193320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}