Journal of Gastroenterology最新文献

{"title":"Why are disorders of gut-brain interaction (DGBI) often food-related? Duodenal eosinophils and mast cells, small intestinal bacteria, food allergy and altered food intake in functional dyspepsia and the irritable bowel syndrome: a new paradigm.","authors":"Nicholas J Talley, Kerith Duncanson, Georgina M Williams","doi":"10.1007/s00535-025-02268-2","DOIUrl":"https://doi.org/10.1007/s00535-025-02268-2","url":null,"abstract":"<p><p>The underlying causes of irritable bowel syndrome (IBS) and functional dyspepsia (FD) have remained largely elusive, but emerging data suggest immune activation and loss of small intestinal homeostasis may explain a major subgroup. FD and IBS symptoms often overlap and may occur early in the post-prandial period, suggesting the origin of symptoms may be much higher in gastrointestinal tract than colon. There is strong evidence low-grade duodenal inflammation, comprising eosinophils and/or mast cells associated with increased permeability, is present at least in a major subset with FD and IBS. This hypothesis is further supported by evidence of circulating increased small intestinal homing T cells and altered duodenal microbiota. We hypothesize a major etiologic pathway whereby interaction of food with intestinal bacteria switches on small intestinal immune activation in FD and IBS leading to presentation of antigens to the mucosa. While the low FODMAP diet provides symptom relief in both IBS and FD, this diet notably also reduces common food protein antigens (e.g., wheat, milk, soy) and urinary histamine levels. The obvious but often overlooked fact that food ingestion usually requires the act of eating adds nuance to determining whether food components or eating itself induces symptoms and that both need to be considered in DGBI in clinical practice. The exciting observations about subtle inflammation in DGBIs offer hope for new diagnostic biomarkers, and if considered in the context of altered dietary patterns and validated against symptom responses, will pave the way for novel DGBI treatment options.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"VPS45 promotes the progression of hepatocellular carcinoma by recycling β1 integrin to the cell membrane via the endocytic pathway.","authors":"Takashi Ofuchi, Hajime Otsu, Kiyotaka Hosoda, Tomohiko Ikehara, Akinori Tsujimoto, Satoshi Higuchi, Shohei Shibuta, Yuya Ono, Kosuke Hirose, Yasuo Tsuda, Yusuke Yonemura, Takaaki Masuda, Hiromitsu Hayashi, Masaaki Iwatsuki, Koshi Mimori","doi":"10.1007/s00535-025-02278-0","DOIUrl":"10.1007/s00535-025-02278-0","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) is a highly aggressive malignancy with poor prognosis, which is often driven by chromosomal amplifications at 1q. Vacuolar sorting protein 45 (VPS45), a gene located on chromosome 1q, is involved in the endocytic recycling pathway; however, its role in HCC remains unclear. In this study, we aimed to investigate the functional significance of VPS45 in the progression of HCC.</p><p><strong>Methods: </strong>VPS45 expression was analyzed using public databases, clinical HCC samples, and cell lines. Functional assays, including VPS45 knockout and rescue experiments, were conducted to assess the effect on tumor progression in vitro and in vivo. The molecular mechanisms underlying VPS45 function, particularly its role in β1 integrin recycling and FAK-AKT signaling activation, were also explored.</p><p><strong>Results: </strong>VPS45 expression was significantly elevated in HCC owing to DNA copy number amplification and correlated with poor prognosis. Moreover, VPS45 knockout suppressed cell proliferation, migration, and invasion, while promoting apoptosis. VPS45 interacted with syntaxin16 and rabenosyn-5 to facilitate the recycling of β1 integrin to the cell membrane, thereby activating FAK-AKT signaling, which promotes oncogenic phenotypes. In xenograft models, VPS45 knockout significantly suppressed tumor growth, further supporting its role in HCC progression.</p><p><strong>Conclusions: </strong>VPS45 is a key oncogene in HCC that promotes tumor progression by enhancing β1 integrin recycling and activating FAK-AKT signaling. Given its strong association with poor prognosis and tumor malignancy, VPS45 may serve as a promising prognostic biomarker and a potential therapeutic target for HCC.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144333267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pretreatment serum angiopoietin-2 predicts prognosis and liver functional reserve after successful HCV eradication with sofosbuvir and velpatasvir in patients with HCV-related decompensated cirrhosis.","authors":"Naoki Kawagishi, Goki Suda, Yuki Tahata, Hayato Hikita, Takahiro Kodama, Satoshi Mochida, Nobuyuki Enomoto, Seiichi Mawatari, Hidekatsu Kuroda, Daiki Miki, Masayuki Kurosaki, Yoichi Hiasa, Norifumi Kawada, Taro Yamashita, Hiroshi Yatsuhashi, Hitoshi Yoshiji, Naoya Kato, Taro Takami, Hisamitsu Miyaaki, Kentaro Matsuura, Yasuhiro Asahina, Yoshito Itoh, Ryosuke Tateishi, Yasunari Nakamoto, Eiji Kakazu, Shuji Terai, Masahito Shimizu, Yoshiyuki Ueno, Norio Akuta, Masatsugu Ohara, Naoya Sakamoto, Tetsuo Takehara","doi":"10.1007/s00535-025-02275-3","DOIUrl":"10.1007/s00535-025-02275-3","url":null,"abstract":"<p><strong>Background: </strong>Direct-acting-antivirals (DAAs) achieve high sustained-virologic response (SVR) rates, even in patients with hepatitis C virus (HCV)-related decompensated liver cirrhosis (LC). However, predictors of post-treatment liver function improvement and survival remain unclear. This study evaluated pretreatment angiopoietin-2 (Ang2) levels as a predictor of prognosis and liver functional reserve after DAA treatment.</p><p><strong>Methods: </strong>This multicenter retrospective study included 123 patients with HCV-related decompensated LC treated with sofosbuvir/velpatasvir. Serum Ang2 levels were quantified, and liver function was assessed using the Child-Pugh grading at baseline and 12 weeks after the end of treatment (SVR12). Factors associated with prognosis and post-SVR liver functional reserve (Child-Pugh grade C) were investigated.</p><p><strong>Results: </strong>Multivariate Cox regression analysis revealed that, in addition to age and creatinine levels at SVR12, baseline Ang2 levels (hazard ratio [HR] = 1.151 per 1000 pg/mL, P = 0.033) and Child-Pugh grade C at SVR12 (HR = 11.765, P < 0.001), but not baseline Child-Pugh grade C, were significantly associated with the overall survival. Multivariate analysis revealed that baseline Ang2 levels and baseline Child-Pugh grade C were significantly and independently associated with Child-Pugh grade C at SVR12. The combination of elevated baseline Ang2 levels (≥ 8684 pg/mL; 1 point) and baseline Child-Pugh grade C (1 point) effectively stratified patients with a high likelihood of having Child-Pugh Grade C at SVR12. The incidence rates were as follows: 0 points, 2.1% (2/96); 1 point, 37.5% (9/24); and 2 points, 100% (2/2) (P < 0.001).</p><p><strong>Conclusions: </strong>Pretreatment Ang2 levels predict survival and liver functional reserve after SVR in HCV-related decompensated LC.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AI-assisted diagnosis of Helicobacter pylori infection: strengths, limitations, and future directions.","authors":"Amir Farah, Amir Mari","doi":"10.1007/s00535-025-02276-2","DOIUrl":"https://doi.org/10.1007/s00535-025-02276-2","url":null,"abstract":"","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144325956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clarifying diagnostic scope and future perspectives in AI-assisted diagnosis of Helicobacter pylori infection.","authors":"Guang Li, Katsuhiro Mabe, Miki Haseyama","doi":"10.1007/s00535-025-02277-1","DOIUrl":"https://doi.org/10.1007/s00535-025-02277-1","url":null,"abstract":"","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"aGenome-scale activation screen reveals lncRNA HNF1A-AS1 promotes pancreatic cancer metastasis through interacting with U2SURP to increase CD44 alternative splicing.","authors":"Shan Lei, Zhixue Zhang, Zhirui Zeng, Wenpeng Cao, Yating Sun, Dahuan Li, Jigang Pan, Yingmin Wu, Tuo Zhang, Tengxiang Chen","doi":"10.1007/s00535-025-02272-6","DOIUrl":"https://doi.org/10.1007/s00535-025-02272-6","url":null,"abstract":"<p><strong>Background: </strong>Pancreatic cancer (PC) has a strong ability to invade and metastasize, which has brought insurmountable obstacles to the treatment of PC. Exploring the molecular mechanism of PC metastasis is still the focus of PC research. The purpose of this study was to explore the molecular mechanism of long noncoding RNA HNF1A-AS1 in promoting PC metastasis, hoping to provide help for the diagnosis and treatment of PC.</p><p><strong>Methods: </strong>CRISPR/CRISPR-associated protein 9 (Cas9) single-guide RNA (sgRNA)-pooled lncRNA libraries were used to screen for the critical lncRNAs regulating PC metastasis. Investigation into HNF1A-AS1's impact on PC cell migration and invasion were conducted through both loss-of-function and gain-of-function approaches. A range of techniques, including fluorescence in situ hybridization (FISH), mRNA sequencing, bioinformatics analysis, dual-luciferase reporter assays, RNA pull-down assays, ChIP-PCR, and rescue assay to explore the regulatory mechanism of HNF1A-AS1 in PC metastasis.</p><p><strong>Results: </strong>SNAI2 activates HNF1A-AS1 transcription. HNF1A-AS1 recruits U2SURP (RRM-dependent domain-dependent) through the 1001-1500 nt region (BR3) to form a functional complex (SNAI2-lncRNA HNF1A-AS1-U2SURP) within the nucleus of PC cells, specifically promoting alternative splicing of CD44 pre-mRNA, transforming it from standard isoform CD44s-CD44v (3-10) isoform, thereby promoting PC invasion and metastasis.</p><p><strong>Conclusions: </strong>This study revealed for the first time that SNAI2 activates the transcription of HNF1A-AS1, and HNF1A-AS1 promote U2SURP to regulate the alternative splicing of CD44 pre-mRNA, causing it to produce a large number of CD44v (3-10) isoforms, thereby promoting the invasion and metastasis of PC.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distinct age-related effects of homologous recombination deficiency on genomic profiling and treatment efficacy in gastric cancer.","authors":"Yoshie Maki, Yoshiyasu Kono, Toshiki Ozato, Hideki Yamamoto, Akira Hirasawa, Daisuke Ennishi, Shuta Tomida, Shinichi Toyooka, Kenta Hamada, Masaya Iwamuro, Seiji Kawano, Motoyuki Otsuka","doi":"10.1007/s00535-025-02267-3","DOIUrl":"https://doi.org/10.1007/s00535-025-02267-3","url":null,"abstract":"<p><strong>Background: </strong>The incidence of gastric cancer among younger patients is increasing globally, with growing attention being paid to the role of homologous recombination deficiency (HRD). However, the effect of HRD on treatment outcomes and prognosis in this population remains unclear.</p><p><strong>Methods: </strong>We analyzed clinical and genomic data from the Center for Cancer Genomics and Advanced Therapeutics database. Younger patients (≤ 39 years, n = 140) were compared with older patients (≥ 65 years, n = 1118) diagnosed with gastric cancer. This study focused on mutations in homologous recombination repair (HRR) genes and their association with tumor mutation burden (TMB), microsatellite instability (MSI), and treatment outcomes.</p><p><strong>Results: </strong>In older patients, HRD was associated with higher TMB and microsatellite instability-high (MSI-H) status, whereas no such correlations were observed in younger patients. Notably, MSI-H status was not observed in the younger group. Younger patients with HRD had a significantly shorter time to treatment failure (TTF) and overall survival (OS) than those without HRD. Conversely, in older patients, there was no significant difference in TTF or OS based on HRD status.</p><p><strong>Conclusion: </strong>HRR gene mutations influence genomic profiling, TMB, and MSI differently depending on the age of gastric cancer onset, suggesting potential effects on treatment efficacy and prognosis.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Asia Pacific Gastroesophageal Cancer Congress (APGCC) 2024 consensus statement on stage 2 and 3 locally advanced gastric and Siewert 3 junctional adenocarcinoma.","authors":"Yoshio Masuda, Kang Ler Fong, Danson Yeo, Charleen Yeo, Koy Min Chue, Said Bani Araba, Chiew Woon Lim, Baldwin Yeung, June Lee, Jinlin Lin, Claramae Chia, Matthew Ng, Kennedy Ng, Jens Samol, Daryl Chia, Jun Liang Teh, Raghav Sundar, Wei-Peng Yong, Hon Lyn Tan, Kei Muro, Florian Lordick, Zev Wainburg, Bo Chuan Tan, Guowei Kim, Koichi Suda, Simon Law, Takeshi Sano, Ramesh Gurunathan, Philip Chiu, Emile Woo, Cuong Duong, Han-Kwang Yang, Vo Duy Long, Hyung Ho Kim, Han Alexander Mahendren, Hyuk Joon Lee, Inian Samarasam, Takuji Gotoda, Reis Liew, Asim Shabbir, Myint Oo Aung, Masanori Terashima, Edward Cheong, Jimmy So, Jeremy Tan","doi":"10.1007/s00535-025-02266-4","DOIUrl":"https://doi.org/10.1007/s00535-025-02266-4","url":null,"abstract":"<p><strong>Background: </strong>While the development in multimodal therapies has helped improve treatment outcomes for patients with locally advanced gastric adenocarcinoma (LAGC), there still exist disparities in opinion with an optimal treatment plan. This consensus hopes to provide clinicians with structured guidelines to aid in the decision-making for treatment options for LAGC.</p><p><strong>Methods: </strong>The consensus statement was initiated by establishing a taskforce in collaboration with the Asia Pacific Gastroesophageal Cancer Congress (APGCC) and a multidisciplinary expert panel was selected. Clinical questions on LAGC where perceived variance in practice or opinion may exist were formulated. Studies involving patients with Stage 2 or 3 gastric or Siewert 3 junctional cancers with treatment arms of perioperative chemotherapy, neoadjuvant chemotherapy, adjuvant chemotherapy, immunotherapy and surgery were included. A total of two rounds of voting were performed. Consensus was determined to be reached when a single answer or a combination of either \"strongly agree/agree\" or \"strongly disagree/disagree\" responses exceeded 75%.</p><p><strong>Results: </strong>A total of thirteen clinical questions were developed. They were identified through five main categories: Distal LAGC, Proximal LAGC, Deficient mismatch repair tumors, Chemotherapy and Immunotherapy, and Elderly/Unfit patients. After two rounds of voting by our multidisciplinary expert panel, eleven out of a total thirteen clinical questions had reached consensus. No consensus was reached for two clinical questions.</p><p><strong>Conclusion: </strong>The APGCC consensus statement aims to guide clinicians in the treatment options for LAGC and Siewert 3 junctional cancer and has clarified some of the roles of perioperative chemotherapy and immunotherapy.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The 2024 diagnostic criteria for primary sclerosing cholangitis.","authors":"Itaru Naitoh, Hiroyuki Isayama, Nobuhisa Akamatsu, Suguru Mizuno, Toshio Fujisawa, Nobuhiro Nakamoto, Yousuke Nakai, Shuichiro Umetsu, Mitsuyoshi Suzuki, Shintaro Yagi, Hironori Haga, Kenji Notohara, Katsuhiro Sano, Susumu Tazuma, Takahiro Nakazawa, Atsushi Tanaka","doi":"10.1007/s00535-025-02265-5","DOIUrl":"https://doi.org/10.1007/s00535-025-02265-5","url":null,"abstract":"<p><p>Primary sclerosing cholangitis (PSC) is an idiopathic chronic cholestatic disease with a poor prognosis. As there were no specific biomarkers for diagnosing PSC, we developed diagnostic criteria in 2016 based on cholangiography and elevated biliary enzymes. Novel findings and knowledge have subsequently accumulated, and we now propose the 2024 diagnostic criteria, to overcome several limitations of the 2016 diagnostic criteria. The Intractable Hepato-Biliary Diseases Study Group in Japan of the Committee of Research on Measures for Intractable Diseases established a working group consisting of experts in PSC comprising gastroenterologists, endoscopists, hepatologists, liver-transplant surgeons, pediatric hepatologists, pathologists, and radiologists. This working group proposed the 2024 diagnostic criteria after several discussions and public hearings. There are additional diagnostic targets; small duct PSC, pediatric PSC, and PSC recurrence following liver transplantation differ from the 2016 diagnostic criteria, which were for diagnosing large duct PSC in adults. The 2024 diagnostic criteria facilitate the use of magnetic resonance cholangiography in addition to endoscopic retrograde cholangiography in imaging, and incorporate gamma-glutamyl transferase for evaluating cholestasis to diagnose pediatric patients. Furthermore, PSC recurrence following liver transplantation can be diagnosed based on a liver biopsy and characteristic biliary findings. We hope that the 2024 diagnostic criteria will help not only hepatologists treating adults but also general physicians, pediatric hepatologists, and liver-transplant surgeons who manage patients with various forms of PSC.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144275105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of liver cancer cell growth by metabolites S-adenosylmethionine and nicotinic acid originating from liver progenitor cells.","authors":"Wen-Ming Liu, Cai-Yang Chen, Hong-Qian Ma, Qiu-Qiu Zhang, Xu Zhou, Yu-Ling Wu, Wei-Jian Huang, Xiao-Shu Qi, Yu-Xin Zhang, Dan Tang, Han-Yong Sun, Hong-Ping Wu, Ying-Fu Jiao, Zhi-Ying He, Wei-Feng Yu, He-Xin Yan","doi":"10.1007/s00535-025-02226-y","DOIUrl":"10.1007/s00535-025-02226-y","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC), the most common form of liver cancer, presents a challenging malignancy with scarce treatment options. Liver progenitor cells (LPCs) play a pivotal role in both liver regeneration and the progression of liver cancer, yet the specific functions of LPCs from different origins in liver cancer remain to be fully elucidated.</p><p><strong>Methods: </strong>We explored the liver progenitor-like cells derived from human hepatocytes (HepLPCs) on the proliferation of HCC both in vitro and in vivo. The mitochondrial function was assessed through electron microscopy and functional experiments. Transcriptomic sequencing and western blot unveiled the fundamental mechanisms at play, whereas metabolomic sequencing pinpointed crucial effector molecules involved in the paracrine secretion of HepLPCs.</p><p><strong>Results: </strong>By employing a co-culture system of HepLPCs and HCC cells, we found that HepLPCs markedly inhibited HCC growth by prompting mitochondrial dysfunction, which further led to the co-inhibition of the Notch1 and JAK1/STAT3 signaling pathways through paracrine actions involving S-adenosylmethionine (SAM) and Nicotinic acid (NA).</p><p><strong>Conclusions: </strong>This study has uncovered that HepLPCs have a suppressive influence on the proliferation of HCC cells. This is achieved through the impairment of mitochondrial function and the inhibition of key signaling pathways, namely, Notch1 and JAK1/STAT3, which are critical drivers of cancer progression. The secretion of the metabolites SAM and NA by HepLPCs appears to be instrumental in mediating these effects. These findings provide a solid foundation for identifying new therapeutic targets and clarifying the mechanisms through which HepLPCs can be harnessed to effectively treat HCC.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"754-769"},"PeriodicalIF":6.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12095412/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143523281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}