World Journal of Gastroenterology最新文献

{"title":"Fecal microbiota transplantation: A promising treatment strategy for chronic liver disease.","authors":"Lei Ma, Meng-Han Zhang, Yi-Fan Xu, Yan-Xu Hao, Xuan-Xuan Niu, Yan Li, Hui-Chun Xing","doi":"10.3748/wjg.v31.i28.105089","DOIUrl":"10.3748/wjg.v31.i28.105089","url":null,"abstract":"<p><p>Chronic liver disease has become a global health crisis, with increasing incidence and mortality rates placing a substantial burden on healthcare systems worldwide. A key factor in the progression of chronic liver disease is intestinal microbiota dysbiosis, which influences liver function <i>via</i> the intricate liver-gut axis. This axis plays a central role in various physiological processes, and disruptions in microbial composition can exacerbate liver pathology. Fecal microbiota transplantation (FMT) has emerged as a promising therapeutic strategy, with the potential to restore the composition and metabolic functions of the intestinal microbiota. Supported by encouraging findings from clinical trials and animal studies, FMT has demonstrated therapeutic benefits, including improvements in clinical symptoms, objective indicators, and long-term prognosis. These benefits encompass reductions in hepatic lipid deposition and inflammation, mitigation of complications in advanced liver disease, promotion of hepatitis B e antigen seroconversion, and enhancement of cognitive function. Although clinical evidence remains preliminary, current data underscore the transformative potential of FMT in managing chronic liver diseases. Nonetheless, challenges persist, including the need for standardized procedures, variability among donors, potential risks, and concerns regarding long-term safety. This review provides a comprehensive evaluation of the current literature on the efficacy and safety of FMT, while exploring future research directions to expand its application in liver disease management.</p>","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":"31 28","pages":"105089"},"PeriodicalIF":5.4,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12305158/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144754538","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":"Efficacy and safety of triple therapy with vonoprazan for <i>Helicobacter pylori</i> eradication: A multicenter, prospective, randomized controlled trial.","authors":"Rong-Shuang Han, Jing-Wen Hao, Tong Wang, Zhi Xin, Guang-Xue Fan, Guo-Dong Wang, Miao-Miao Liu, Cheng-Xia Liu, Qiu-Zi Yang, Zheng-Wu Yang, Xiao-Yan Lv, Chao Zhang, Gang Bian, Jing Meng, Zhen-Qin Cui, Xiao-Jing Yun, Jian-Hua Cao, Shu-Hui Li, Jia-Feng Fan, Hong-Gang Ma, Feng-Yu Gao, Tao Mao, Zi-Bin Tian, Xiao-Hui Song, Ya-Nan Yu","doi":"10.3748/wjg.v31.i28.109001","DOIUrl":"10.3748/wjg.v31.i28.109001","url":null,"abstract":"<p><strong>Background: </strong><i>Helicobacter pylori</i> (<i>H. pylori</i>) is a Gram-negative bacterium that relies on flagellar motility to colonize the stomach, damaging the gastric mucosa through various mechanisms and leading to various digestive disorders. Accurate assessment and precise treatment are essential in initial intensive therapy.</p><p><strong>Aim: </strong>To investigate the efficacy and safety of a vonoprazan (VPZ)-based triple regimen for first-line eradication of <i>H. pylori</i> in China.</p><p><strong>Methods: </strong>This multicenter noninferior randomized controlled trial (June 2022 to November 2023) involved 524 <i>H. pylori</i>-positive patients across 19 centers in Shandong, China. Participants were randomized to 14-day esomeprazole/bismuth/amoxicillin/clarithromycin (EBAC), 14-day VPZ/amoxicillin/clarithromycin (VACa), or 10-day VPZ/amoxicillin/clarithromycin (VACb) - all administered twice daily. Primary outcomes (eradication rates) were assessed <i>via</i> intention-to-treat (ITT) and per-protocol (PP) analyses. Secondary endpoints included adverse events and adherence. Noninferiority testing and <i>χ</i> ² tests were used for statistical comparisons.</p><p><strong>Results: </strong>A total of 524 patients participated in this study. In ITT analysis, the eradication rates of the EBAC, VACa, and VACb groups were 72.6% (127/175), 88.0% (154/175), and 83.3% (145/174), respectively (<i>P</i> = 0.001). The difference in the eradication rate between the EBAC and VPCa groups was 15.4% [95% confidence interval (CI): 7.3-23.6, <i>P</i> < 0.001], and that between the EBAC and VACb groups was 10.8% (95%CI: 2.1-19.4, <i>P</i> = 0.018). In PP analysis, the eradication rates of the EBAC, VACa, and VACb groups were 81.4% (127/156), 93.9% (154/164), and 90.6% (145/160), respectively (<i>P</i> = 0.001). There was no significant difference in the incidence of adverse reactions among the three groups, which were 36.6%, 33.8% and 29.6%, respectively (<i>P</i> = 0.50).</p><p><strong>Conclusion: </strong>VPZ-based triple therapies demonstrate noninferiority to 14-day bismuth-containing regimens, with the 10-day regimen showing comparable efficacy and similar adverse event rates.</p>","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":"31 28","pages":"109001"},"PeriodicalIF":5.4,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12305142/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144754536","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":"Duodenal mucosal ablation: An emerging therapeutic concept for metabolic dysfunction-associated fatty liver disease.","authors":"Cornelius J Fernandez, Sweekruti Jena, Vijaya Lakshmi, Joseph M Pappachan","doi":"10.3748/wjg.v31.i28.109468","DOIUrl":"10.3748/wjg.v31.i28.109468","url":null,"abstract":"<p><p>Metabolic dysfunction-associated fatty liver disease (MAFLD) is currently the leading cause of end-stage liver disease and liver cancer in the world because of the obesity pandemic. Insulin resistance resulting from abdominal adiposity is the main cause of MAFLD and type 2 diabetes mellitus among these patients. Although very common, therapeutic options for MAFLD are currently limited. Metabolic and bariatric surgery is the best treatment option for weight loss that can also improve MAFLD in a very high proportion of patients. However, surgical interventions are expensive, technically challenging, and carry significant immediate and long-term postoperative risks. Duodenal mucosal ablation, a malabsorptive endoscopic bariatric intervention, has shown beneficial effects in the management of obesity with an improvement of insulin resistance. It alters the duodenal mucosal lining, which helps maintain cellular homeostasis and better intestinal endocrine function. This process helps reduce lipid deposition in the liver, maintain serum lipid levels, and promote weight loss, especially in patients with type 2 diabetes mellitus-related MAFLD. However, some of these effects were independent of weight loss and food intake. As a minimally invasive procedure, it is beneficial for patients who have not had success with drug therapy alone, though this approach needs to be tested and further developed in future clinical trials. A basic study by Yu <i>et al</i> in the recent issue of the <i>World Journal of Gastroenterology</i> on duodenal mucosal ablation using irreversible electroporation, when experimented on rats, has shown fewer complications compared to other metabolic surgeries. This editorial describes the minimally invasive endoscopic bariatric strategies for the management of obesity and MAFLD in light of this experimental study.</p>","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":"31 28","pages":"109468"},"PeriodicalIF":5.4,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12305128/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144754534","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":"Gastrointestinal tract, its pathophysiology and <i>in-vitro</i> models: A \"quick\" reference guide to translational studies.","authors":"Kristijan Skok, Boštjan Vihar, Uroš Maver, Lidija Gradišnik, Konstantin Bräutigam, Martin Trapecar, Pavel Skok","doi":"10.3748/wjg.v31.i28.108297","DOIUrl":"10.3748/wjg.v31.i28.108297","url":null,"abstract":"<p><p>The gastrointestinal (GI) tract is essential for digestion, absorption, excretion, and protection, supported by a diverse microbial ecosystem. Traditional <i>in-vitro</i> models often fall short in capturing the physiological complexity of the GI tract, limiting their translational applications. A comprehensive approach is needed to bridge the gap between simple cell cultures and more complex systems used in translational research. This review explores the limitations of conventional two-dimensional cell cultures and emphasizes the emerging use of three-dimensional and microfluidic systems that better replicate the GI tract's structure and functions. It highlights the importance of incorporating patient-derived cells and engineered microenvironments to enhance model relevance and support personalized medicine. The review also discusses advanced fabrication techniques such as micro-extrusion and laser-assisted bioprinting, which enable the creation of sophisticated tissue models capable of simulating critical GI processes, including molecular transport, peristalsis, and liver coupling. Advancing the complexity of <i>in-vitro</i> systems will help replicate the GI tract's interactions and physiological phenomena, thus improving the translational potential of GI research. This review provides valuable insights into the advancements and challenges in GI modeling, serving as a comprehensive guide for developing models that bridge the gap between basic cell cultures and clinically relevant systems.</p>","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":"31 28","pages":"108297"},"PeriodicalIF":5.4,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12305151/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144754539","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":"Ascites characteristics in acute pancreatitis: A prognostic indicator of organ failure and mortality.","authors":"Jing-Wen Rao, Jia-Rong Li, Yao Wu, Tian-Ming Lai, Zhen-Gang Zhou, Yue Gong, Ying Xia, Ling-Yu Luo, Liang Xia, Wen-Hao Cai, Wei Huang, Yin Zhu, Wen-Hua He","doi":"10.3748/wjg.v31.i28.108926","DOIUrl":"10.3748/wjg.v31.i28.108926","url":null,"abstract":"<p><strong>Background: </strong>Acute pancreatitis (AP) is a severe condition, and abdominal effusion is a significant predictor of its severity and prognosis. However, the relationship between ascites characteristics and AP outcomes remains undefined.</p><p><strong>Aim: </strong>To assess the correlation between ascites characteristics and clinical prognosis in AP patients by comparing color depth and turbidity of early ascites.</p><p><strong>Methods: </strong>This study included 667 AP patients with ascites, categorized by color and turbidity into yellow clear (<i>n</i> = 54), yellow turbid (<i>n</i> = 293), red brown (<i>n</i> = 320). The trend <i>χ</i> ² test was employed to analyze the incidence of organ failure (OF), infected pancreatic necrosis (IPN), and mortality across groups. Receiver operating characteristic (ROC) curves were used to evaluate the predictive value of ascites cell count, amylase, protein, and lactate dehydrogenase (LDH) for abdominal compartment syndrome (ACS) and intra-abdominal hemorrhage.</p><p><strong>Results: </strong>AP patients with ascites exhibited higher scores of scoring systems (such as Bedside index for severity in AP, Acute Physiology and Chronic Health Examination II, <i>etc.</i>) and increased complications and mortality rates (all <i>P</i> < 0.05) compared to those without ascites. A linear association was observed between ascites color depth and turbidity and the incidence of OF, pancreatic necrosis, IPN, and mortality (<i>P</i> < 0.05). LDH in ascites demonstrated high accuracy in predicting ACS and intra-abdominal hemorrhage, with areas under the ROC curve of 0.77 and 0.79, respectively.</p><p><strong>Conclusion: </strong>Early in AP, ascites correlates with OF, IPN, and mortality, showing linear associations with color depth and turbidity. Ascitic LDH reliably predicts ACS and intra-abdominal hemorrhage in AP patients.</p>","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":"31 28","pages":"108926"},"PeriodicalIF":5.4,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12305166/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144754520","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":"Efficacy and safety of transcatheter arterial chemoembolization combined with microwave ablation for hepatic hemangiomas (> 5 cm).","authors":"Jia-Peng Sun, Kang Zhou, Jie Pan, Ning Yang, Xiao-Nan Sun, Hai-Tao Zhao, Xiao-Bo Yang","doi":"10.3748/wjg.v31.i28.109078","DOIUrl":"10.3748/wjg.v31.i28.109078","url":null,"abstract":"<p><strong>Background: </strong>Hepatic hemangiomas represent the most prevalent benign liver tumors. Surgical management of large symptomatic hepatic hemangiomas remains controversial and there is an increasing interest in minimally invasive techniques, such as transcatheter arterial chemoembolization (TACE) and microwave ablation (MWA).</p><p><strong>Aim: </strong>To evaluate the efficacy and safety of TACE combined with MWA for large hepatic hemangiomas.</p><p><strong>Methods: </strong>This retrospective cohort study was conducted at Peking Union Medical College Hospital between January 2015 and January 2024. Eighty-two patients with hepatic hemangiomas > 5 cm were divided into two groups: Observation (TACE + MWA, <i>n</i> = 50) and control (TACE, <i>n</i> = 32). Tumor diameter and treatment outcomes were evaluated at baseline, 12 months, and > 3 years. Appropriate statistical tests were chosen based on the type and distribution of the data.</p><p><strong>Results: </strong>At baseline, the median tumor diameter was 8.3 (range: 5.0-19.2) cm in the observation group and 8.5 (range: 5.0-20.0) cm in the control group. The median follow-up duration was 44.6 (95% confidence interval: 36.7-52.5) months. At 12 months post-treatment, the observation group demonstrated a higher tumor reduction ratio compared to the control group (50.98% <i>vs</i> 23.28%, respectively; <i>P</i> < 0.001). The objective response rate was 93.94% in the observation group, which was significantly higher than that in the control group (33.33%) (<i>P</i> < 0.001). No recurrence occurred in the observation group, while one case occurred in the control group. Notably, no cases of hemoglobinuria or acute kidney injury were reported in the observation group.</p><p><strong>Conclusion: </strong>Combination treatment enhances tumor shrinkage, promotes long-term tumor control, and reduces the complications associated with MWA, thereby presenting a promising alternative to surgical resection.</p>","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":"31 28","pages":"109078"},"PeriodicalIF":5.4,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12305182/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144754535","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":"Clinicopathological significance of histological diversity in gastric adenocarcinoma with primitive enterocyte phenotype: A methylation-driven aggressive entity.","authors":"Hou-Qiang Li, Lan-Qing Zheng, Wen-Tao Huang, Xun-Bin Yu, Xia Zhang, Lan Lin, Shan-Shan Lv, Xi-Yao Yan, Xiao-Yan Chen","doi":"10.3748/wjg.v31.i28.108990","DOIUrl":"10.3748/wjg.v31.i28.108990","url":null,"abstract":"<p><strong>Background: </strong>Gastric adenocarcinoma with primitive phenotypes has recently attracted increasing attention due to its aggressive nature and challenging diagnosis. Gastric adenocarcinoma with enteroblastic differentiation (GAED) and hepatoid adenocarcinoma (HAC) were previously regarded as gastric adenocarcinoma with primitive enterocyte phenotype (GAPEP). GAPEP is known for its poor prognosis, and the accurate diagnosis of GAPEP directly affects therapeutic decision-making. Despite their poor prognosis and morphological heterogeneity, the molecular drivers of GAPEP, particularly methylation-driven mechanisms, remain poorly explored.</p><p><strong>Aim: </strong>To investigate the clinicopathological and molecular characteristics of GAPEP and establish an integrative diagnostic strategy to guide therapeutic decision-making.</p><p><strong>Methods: </strong>Based on the expression profile and morphology, patients were divided into three groups: GAPEP (including GAED and HAC), conventional gastric cancer (CGC), and CGC expressing primitive phenotypic markers. We analyzed clinicopathological features and overall survival. Data from The Cancer Genome Atlas were also analyzed, and functional enrichment analysis was conducted.</p><p><strong>Results: </strong>GAPEP showed diverse morphology, and immunohistochemical staining alone was not adequate for accurate diagnosis. Histologically, GAPEP was characterized by large, polygonal tumor cells with supranuclear or subnuclear vacuoles, a \"piano keyboard-like\" appearance, and clear or eosinophilic cytoplasms. Compared to CGC and CGC expressing primitive phenotypic markers, GAPEP displayed more aggressive clinical features. Molecular analysis showed significant differences in molecular subtypes, <i>TP53</i> mutation, <i>ERBB2</i> amplification, <i>ARID1A</i> mutation, MSI status, and CpG island methylator phenotype category. Genomic analysis revealed that <i>TP53</i> mutations, <i>APC</i> mutations, and <i>ERBB2</i> amplifications were more frequent in GAPEP. Genes involved in methylation processes were highly upregulated in GAPEP. HAC and GAED shared similar clinicopathological and genetic characteristics. Functional enrichment analysis highlighted the critical role of methylation in the development of GAPEP.</p><p><strong>Conclusion: </strong>The diversity and aggressiveness of GAPEP are driven by deregulated methylation, necessitating the integration of morphological and immunohistochemical diagnosis. Targeting methylation can provide new therapeutic opportunities for treating this aggressive cancer.</p>","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":"31 28","pages":"108990"},"PeriodicalIF":5.4,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12305129/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144754532","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":"Construction of a community-based primary screening and hospital-based confirmatory screening pathway in pediatric nonalcoholic fatty liver disease.","authors":"Ming-Jie Yao, Yun-Fei Xing, Shu-Hong Liu, Ya-Fei Peng, Shu-Han Yang, Juan-Juan Chen, Jing-Min Zhao, Hui Wang","doi":"10.3748/wjg.v31.i28.108321","DOIUrl":"10.3748/wjg.v31.i28.108321","url":null,"abstract":"<p><strong>Background: </strong>Fibrosis is a critical event in the progression of pediatric nonalcoholic fatty liver disease (NAFLD).</p><p><strong>Aim: </strong>To develop less invasive models based on machine learning (ML) to predict significant fibrosis in Chinese NAFLD children.</p><p><strong>Methods: </strong>In this cross-sectional study, 222 and 101 NAFLD children with available liver biopsy data were included in the development of screening models for tertiary hospitals and community health centers, respectively. Predictive factors were selected using least absolute shrinkage and selection operator regression and stepwise logistic regression analyses. Logistic regression (LR) and other ML models were applied to construct the prediction models.</p><p><strong>Results: </strong>Simplified indicators of the ATS and BIU indices were constructed for tertiary hospitals and community health centers, respectively. When models based on the ATS and BIU parameter combinations were constructed, the random forest (RF) model demonstrated higher screening accuracy compared to the LR model (0.80 and 0.79 for the RF model and 0.72 and 0.77 for the LR model, respectively). Using cutoff values of 90% for sensitivity and 90% for specificity, the RF models could effectively identify and exclude NAFLD children with significant fibrosis in the internal validation set (with positive predictive values and negative prediction values exceeding 0.80), which could prevent liver biopsy in 60% and 71.4% of NAFLD children, respectively.</p><p><strong>Conclusion: </strong>This study developed new models for predicting significant fibrosis in NAFLD children in tertiary hospitals and community health centers, which can serve as preliminary screening tools to detect the risk population in a timely manner.</p>","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":"31 28","pages":"108321"},"PeriodicalIF":5.4,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12305124/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144754533","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":"Phospholipase D2: A biomarker implicated in various pancreatic diseases beyond acute pancreatitis.","authors":"Ana I Tornel Avelar, Christian Navarro Gerrard, Bryan Adrian Priego Parra","doi":"10.3748/wjg.v31.i28.108271","DOIUrl":"10.3748/wjg.v31.i28.108271","url":null,"abstract":"<p><p>Acute pancreatitis (AP) remains a clinical challenge due to its heterogeneous presentation and potential for rapid progression to severe disease. In their editorial, Wang <i>et al</i> highlight phospholipase D2 (PLD2) as a novel candidate biomarker, proposing its involvement in key inflammatory pathways and its inverse correlation with disease severity. While this represents a promising improvement in precision diagnostics, significant gaps remain that require further investigation. Specifically, the functional role of PLD2 in the molecular cascade of AP is not yet fully understood. Questions still remain, such as: Is the observed downregulation of PLD2 a causal factor or an epiphenomenon? Does PLD2 modulation offer a tangible therapeutic benefit beyond a mere correlation? These questions highlight the necessity of mechanistic <i>in vivo</i> studies to validate the role and therapeutic potential of PLD2. Furthermore, interindividual variability in inflammatory responses raises concerns regarding PLD2's predictive consistency across genetically diverse populations. The temporal dynamics of PLD2 expression in AP also remain unclear; establishing whether its variations precede clinical deterioration is essential for its use in early risk stratification, integrating multiomics research (proteomics, metabolomics, transcriptomics, and lipidomics), which can clarify the biological interactions and regulatory pathways of PLD2 under complex mechanisms. Likewise, well-designed, multicenter, prospective studies will be essential in determining its true clinical value. The research by Wang <i>et al</i> initiates an intriguing direction in the quest for AP biomarkers, but further research is required before PLD2 can be established as a clinically applicable tool. Additional efforts are required to close this gap and define whether its role transcends a mere association in order for it to become a therapeutic target.</p>","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":"31 28","pages":"108271"},"PeriodicalIF":5.4,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12305163/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144754521","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":"FBP1 as a key regulator of focal adhesion kinase-mediated hepatic stellate cell activation: Multi-omics and experimental validation.","authors":"Hua-Yue Wu, Lu Han, Tao Ran, Yong Sun, Qing-Xiu Zhang, Tao Huang, Gao-Liang Zou, Ya Zhang, Yu-Mei Zhou, Guo-Yuan Lin, Shao-Jie Chen, Jing-Lin Wang, Chen Pan, Fan Lu, Hong-Fei Pu, Xue-Ke Zhao","doi":"10.3748/wjg.v31.i28.107361","DOIUrl":"10.3748/wjg.v31.i28.107361","url":null,"abstract":"<p><strong>Background: </strong>Inhibiting hepatic stellate cell (HSC) activation is a key therapeutic strategy in liver fibrosis (LF). During activation, aerobic glycolysis is upregulated to meet increased energy demands. Although focal adhesion kinase (FAK) has been implicated in regulating HSC glycolysis, its precise role in activation remains unclear.</p><p><strong>Aim: </strong>To investigate the effects of FAK and fructose-1, 6-bisphosphatase 1 (FBP1) on LF through the modulation of aerobic glycolysis in HSCs.</p><p><strong>Methods: </strong>Eighteen mice were randomly assigned to three groups: Control, carbon tetrachloride (CCl₄)-induced LF, and CCl₄ with FAK inhibitor treatment. Liver tissues were analyzed using transcriptomic and proteomic sequencing. Differential gene expression, Mfuzz clustering, and protein interaction network analyses identified key regulatory factors. Immunohistochemistry (IHC) and Western blot (WB) analysis were used to assess FAK and FBP1 expression, along with glycolysis-related enzymes. The migratory behavior of HSCs was evaluated using Transwell migration and scratch assays.</p><p><strong>Results: </strong>Transcriptomic and proteomic analyses revealed significantly reduced FBP1 expression in CCl₄-induced fibrosis, which was restored upon FAK inhibition. Histological staining (hematoxylin and eosin, Masson's trichrome, Sirius red) confirmed reduced fibrosis following FAK inhibition. WB analysis demonstrated suppression of glycolysis-related enzymes. In LX-2 cells, FAK inhibition attenuated HSC activation and glycolysis while upregulating FBP1. Exogenous recombinant FBP1 inhibited HSC activation and glycolysis. Transwell and scratch assays showed that FBP1 significantly impaired HSC migration. In addition, WB and IHC analyses confirmed lower FBP1 expression in fibrotic liver tissues from patients compared to healthy controls.</p><p><strong>Conclusion: </strong>FAK inhibitors and increased FBP1 expression inhibit aerobic glycolysis in HSCs, thereby improving LF. Thus, FAK and FBP1 may be potential targets for LF treatment.</p>","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":"31 28","pages":"107361"},"PeriodicalIF":5.4,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12305161/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144754537","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}