Digestion最新文献

{"title":"Surveillance and Endoscopic Resection of Ulcerative Colitis-Associated Neoplasia: A Japanese Perspective.","authors":"Yu Hashimoto, Syota Tomaru, Yuki Itoi, Keigo Sato, Hiroko Hosaka, Hirohito Tanaka, Shiko Kuribayashi, Yoji Takeuchi, Toshio Uraoka","doi":"10.1159/000543250","DOIUrl":"10.1159/000543250","url":null,"abstract":"<p><strong>Background: </strong>Patients with a long history of ulcerative colitis (UC) are at risk of developing a serious complication known as UC-associated neoplasia (UCAN). Because the treatment strategy for UCAN greatly differs from that for sporadic tumors, UCAN needs to be distinguished from sporadic tumors. This article provides an overview of the current status and future challenges regarding the surveillance colonoscopy (SC) and endoscopic submucosal dissection (ESD) of neoplastic lesions in patients with UC.</p><p><strong>Summary: </strong>To reduce the risk of associated mortality, the current guidelines recommend initiating SC using chromoendoscopy with high-definition colonoscopy 8-10 years after the confirmation of a UC diagnosis. However, the endoscopic diagnosis of UCAN is occasionally challenging and requires a stepwise approach using multiple endoscopic modalities. The worldwide consensus is that a diagnosis of high-grade dysplasia or higher is an indication for proctocolectomy. Although the management of low-grade dysplasia (LGD) remains controversial, the SCENIC consensus statement recommends the complete removal of \"endoscopically resectable\" LGD, followed by monitoring. ESD was developed in Japan, allows for the removal of complex gastrointestinal lesions, facilitates the treatment of LGD, and enables precise pathological evaluations to differentiate between UCAN and sporadic tumors and to determine the grade of dysplasia in UCAN. Close endoscopic surveillance should follow complete endoscopic resection. A Japanese expert consensus meeting recommended the performance of follow-up SC 6-12 months after complete resection with ESD.</p><p><strong>Key messages: </strong>The roles of ESD for UCAN are to treat LGD and to enable the histopathological examination of complete excisional biopsy specimens to differentiate between UCAN and sporadic tumors and grade the dysplasia of UCAN. In future, prospective cohort studies are needed to better assess the clinical outcomes of ESD in patients with UC.</p>","PeriodicalId":11315,"journal":{"name":"Digestion","volume":" ","pages":"1-7"},"PeriodicalIF":3.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143406222","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":"Dynamic Observation of Colonic Lesions, Commensal Microbiome and Mycobiome Variations in Trinitrobenzene Sulfonic Acid -Induced Experimental Crohn's Disease in Rats.","authors":"Mingjiang Liu, Huiwen Wang, Junjie Huang, Yuying Huai, Chenglong Yu, Guoqing Fang, Minxia Zhang, Ruonan Bo, Kai Fan, Jingui Li","doi":"10.1159/000543337","DOIUrl":"https://doi.org/10.1159/000543337","url":null,"abstract":"<p><p>Crohn's disease (CD) is an inflammatory bowel disease characterized by chronic inflammation of the entire digestive lining. Although the pathogenesis of CD remains unclear, multiple factors especially altered microbiota are among its causes. In this study, an experimental CD model was established by TNBS-enema. Then the dynamic changes of colonic tissue lesions, tight junctions, inflammation response, and oxidative stress are respectively tested by H&amp;E staining, immunofluorescence staining, and commercial kits. 16S rRNA and ITS sequencing of colonic feces were applied to analyze the composition and diversity of the microbiome and mycobiome for lasting 5 weeks. As a result, despite TNBS being applied only once time, the stimuli-caused injury reached a peak in the second week (the most severe period), after which symptoms began to gradually return to the normal stage. Additionally, consistent with the TNBS-caused colonic damage, deaths were also concentrated within two weeks after modeling, with only one death occurring in the subsequent period despite ongoing inflammation and other typical symptoms. In terms of gut bacteria, microbiome diversity decreased significantly while mycobiome diversity increased, along with the enrichment of harmful microbiota and shrinkage of probiotic microorganisms. Therefore, the data suggested that TNBS-induced CD can be roughly divided into two phases: the acute inflammatory phase (weeks 1 to 2) and the chronic inflammatory phase (weeks 3 to 5). However, the microbiome and mycobiome dysbiosis did not return to normal within the trial period. Hence, our findings may facilitate a better comprehension of the dynamic progress of experimental TNBS-induced CD.</p>","PeriodicalId":11315,"journal":{"name":"Digestion","volume":" ","pages":"1-17"},"PeriodicalIF":3.0,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143398660","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 Interpretation of Magnifying Endoscopy for the Diagnosis of Colorectal Lesions.","authors":"Naohisa Yoshida, Ken Inoue, Elsayed Ghoneem, Yoshikazu Inagaki, Reo Kobayashi, Naoto Iwai, Osamu Dohi, Ryohei Hirose, Yoshito Itoh","doi":"10.1159/000543996","DOIUrl":"10.1159/000543996","url":null,"abstract":"<p><strong>Background: </strong>Accurate endoscopic diagnosis is crucial for determining the appropriate treatment strategy for colorectal lesions, which may include cold snare polypectomy, endoscopic mucosal resection, or endoscopic submucosal dissection.</p><p><strong>Summary: </strong>While white light imaging (WLI) serves as the basic and initial method for endoscopic diagnosis, additional techniques such as narrow band imaging (NBI), blue laser/light imaging (BLI), and magnified observation of pit patterns are necessary when WLI results are inconclusive. These advanced diagnostic methods enable precise differentiation of lesions such as adenoma, T1 cancer, and sessile serrated lesion. Furthermore, recent advancements in endoscopic systems have enhanced image clarity and detail, thereby improving diagnostic accuracy.</p><p><strong>Key messages: </strong>This review provides an in-depth discussion on how magnified endoscopy, utilizing the Japan NBI Expert Team (JNET) classification with NBI/BLI and pit pattern classification with chromoendoscopy, aids in the accurate diagnosis of colorectal lesions.</p>","PeriodicalId":11315,"journal":{"name":"Digestion","volume":" ","pages":"107-114"},"PeriodicalIF":3.0,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188489","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 Progress in the Study of Pathogenesis of Alcoholic Pancreatitis.","authors":"Hanhui Li, Xiaoping Tan, Jie Li, Qing Zhang","doi":"10.1159/000542548","DOIUrl":"https://doi.org/10.1159/000542548","url":null,"abstract":"<p><strong>Background: </strong>Alcoholic pancreatitis is a progressive condition characterized by susceptibility to recurrence, progression to chronic pancreatitis, complications, and high morbidity.</p><p><strong>Summary: </strong>The main causes include long-term alcoholism, excessive drinking, the toxic effects of alcohol metabolites, interactions with biliary diseases, and genetic factors. Alcohol is the second leading cause of acute pancreatitis (AP) in the USA, accounting for one-third of all AP cases. A follow-up study on readmission revealed that the readmission rate of alcoholic acute pancreatitis (AAP) patients within 11 months was 43.1%, of which men dominated the admissions and readmissions of AAP. Among this population, 82.3% have alcohol use disorder, over half have tobacco use disorders, 6.7% have tobacco use disorder, 4.5% have opioid use disorder, and 18.5% of patients exhibit signs of potential alcoholic chronic pancreatitis. Numerous animal and clinical studies suggest that alcohol alone does not cause pancreatitis; rather, additional factors such as smoking, endotoxin lipopolysaccharide (LPS), genetic mutations, or other genetic predispositions - are necessary for the disease's progression.</p><p><strong>Key messages: </strong>Given the high rates of admission and readmission for alcoholic pancreatitis, it is essential to further investigate its pathogenesis and pathological processes to develop more effective treatment strategies. Therefore, this paper summarizes the current understanding of the pathogenesis and treatment status of alcoholic pancreatitis, drawing on recently published literature and data to provide insights and references for future research and treatment efforts.</p>","PeriodicalId":11315,"journal":{"name":"Digestion","volume":" ","pages":"1-15"},"PeriodicalIF":3.0,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002057","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":"Endocuff Vision-Assisted Colonoscopy Significantly Improves Adenoma Detection in a Shorter Withdrawal Time Compared with Standard Colonoscopy: A Randomized Controlled Trial.","authors":"Duc Trong Quach, Thu Anh Nguyen, Mai Ngoc Luu, Uyen Pham-Phuong Vo, Vy Ly-Thao Tran, Truc Le-Thanh Tran, Tai Duy Nguyen, Nhan Quang Le, Toru Hiyama, Shinji Tanaka","doi":"10.1159/000543630","DOIUrl":"10.1159/000543630","url":null,"abstract":"<p><strong>Introduction: </strong>Although several studies in Western countries have shown that Endocuff Vision-assisted colonoscopy (EC) can improve the colorectal adenoma detection rate (ADR), such evidence in Asia is still scarce. This study aimed to evaluate the performance of EC in detecting colorectal adenomas in Vietnamese patients.</p><p><strong>Methods: </strong>This was a randomized controlled trial conducted at a tertiary hospital in Vietnam. Subjects aged ≥18 years referred for colonoscopy for symptomatic investigation or screening were randomly assigned to the EC group or standard colonoscopy (SC) group. The primary outcome was the ADR. The secondary outcomes included the mean number of adenomas per procedure (MAP), cecal intubation time, and withdrawal time.</p><p><strong>Results: </strong>There were 476 participants (241 in the EC group, 235 in the SC group) with a median age of 52 (interquartile range [IR]: 46, 58) years. There were no significant differences between the two groups regarding age, sex, smoking status, family history of colorectal cancer, or indications for colonoscopy. Compared with the SC group, the EC group had significantly higher ADRs (35.7% vs. 22.6%, p = 0.002) and MAPs (0.68 vs. 0.39, p = 0.004). The intubation durations were comparable between the two groups. The withdrawal time in the EC group was shorter than that in the SC group (median [seconds]: 266 [IR: 224, 314] vs. 360 [IR: 310, 390], p < 0.001).</p><p><strong>Conclusions: </strong>Compared with SC, EC significantly increased both the ADR and MAP in a shorter inspection time and could be a better choice for colonoscopy screening.</p>","PeriodicalId":11315,"journal":{"name":"Digestion","volume":" ","pages":"1-11"},"PeriodicalIF":3.0,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002056","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":"Identification of a Novel Activated NK-Associated Gene Score Associated with Diagnosis and Biological Therapy Response in Ulcerative Colitis.","authors":"Siyuan Dong, Yu Zhang, Lingna Ye, Qian Cao","doi":"10.1159/000540939","DOIUrl":"10.1159/000540939","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Natural killer (NK) cells are associated with the pathogenesis of ulcerative colitis (UC); however, their precise contributions remain unclear. The present study aimed to investigate the diagnostic value of the activated NK-associated gene (ANAG) score in UC and evaluate its predictive value in response to biological therapy.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Bulk RNA-seq and scRNA-seq datasets were obtained from the Gene Expression Omnibus (GEO) and Single Cell Portal (SCP) databases. In the bulk RNA-seq, differentially expressed genes (DEGs) were screened by the \"Batch correction\" and \"Robust rank aggregation\" (RRA) methods. The immune infiltration landscape was estimated using single-sample gene set enrichment analysis (ssGSEA) and CIBERSORT. DEGs that correlated with activated NK cells were identified as activated NK-associated genes (ANAGs). Protein-protein interaction (PPI) analysis and least absolute shrinkage and selection operator (LASSO) regression were used to screen key ANAGs and establish an ANAG score. The expression levels of the four key ANAGs were validated in human samples by real-time quantitative polymerase chain reaction (RT-qPCR) and immunofluorescence. The potential therapeutic drugs for UC were identified using the DSigDB database. Through scRNA-seq data analysis, the cell scores based on the ANAGs were calculated by \"AddModuleScore\" and \"AUCell.\"&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Immune infiltration analysis revealed a higher abundance of activated NK cells in noninflamed UC tissues (ssGSEA, p &lt; 0.001; CIBERSORT, p &lt; 0.01). Fifty-four DEGs correlated with activated NK cells were identified as ANAGs. The ANAG score was established using four key ANAGs (SELP, TIMP1, MMP7, and ABCG2). The ANAG scores were significantly higher in inflamed tissues (p &lt; 0.001) and in biological therapy nonresponders (NR) tissues before treatment (golimumab, p &lt; 0.05; ustekinumab, p &lt; 0.001). The ANAG score demonstrated an excellent diagnostic value (AUC = 0.979). Patients with higher ANAG scores before treatment were more likely to experience a lack of response to golimumab or ustekinumab (golimumab, p &lt; 0.05; ustekinumab, p &lt; 0.001).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;This study established a novel ANAG score with the ability to precisely diagnose UC and distinguish the efficacy of biological treatment.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Natural killer (NK) cells are associated with the pathogenesis of ulcerative colitis (UC); however, their precise contributions remain unclear. The present study aimed to investigate the diagnostic value of the activated NK-associated gene (ANAG) score in UC and evaluate its predictive value in response to biological therapy.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Bulk RNA-seq and scRNA-seq datasets were obtained from the Gene Expression Omnibus (GEO) and Single Cell Portal (SCP) databases. In the bulk RNA-seq, differentially expressed genes (DEGs) were screened by the \"Batch correctio","PeriodicalId":11315,"journal":{"name":"Digestion","volume":" ","pages":"1-22"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11825133/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142055178","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":"Evidence-Based Clinical Guidelines for Chronic Constipation 2023.","authors":"Eikichi Ihara, Noriaki Manabe, Hidenori Ohkubo, Naotaka Ogasawara, Haruei Ogino, Kazuki Kakimoto, Motoyori Kanazawa, Hidejiro Kawahara, Chika Kusano, Shiko Kuribayashi, Akinari Sawada, Tomohisa Takagi, Shota Takano, Toshihiko Tomita, Toshihiro Noake, Mariko Hojo, Ryota Hokari, Tatsuhiro Masaoka, Tomohiko Machida, Noboru Misawa, Yoshiyuki Mishima, Hiroshi Yajima, Sayuri Yamamoto, Hiroshi Yamawaki, Tatsuya Abe, Yasumi Araki, Kunio Kasugai, Takeshi Kamiya, Akira Torii, Atsushi Nakajima, Koji Nakada, Shin Fukudo, Yasuhiro Fujiwara, Hiroto Miwa, Hiromi Kataoka, Akihito Nagahara, Kazuhide Higuchi","doi":"10.1159/000540912","DOIUrl":"10.1159/000540912","url":null,"abstract":"&lt;p&gt;&lt;p&gt;The Japan Gastroenterological Association published the first version of its clinical guidelines for chronic constipation 2023. Based on the latest evidence, these guidelines describe the definition, classification, diagnostic criteria, diagnostic testing methods, epidemiology, pathophysiology, and treatment of chronic constipation. They include flowcharts for both diagnosis and treatment of chronic constipation. In the treatment of chronic constipation, the first step involves differentiating between secondary forms, such as organic disease-associated constipation, systemic disease-associated constipation, and drug-induced constipation. The next step is to determine whether the chronic constipation stems from a motility disorder, a form of primary chronic constipation. For functional constipation and constipation-predominant irritable bowel syndrome, treatment should be initiated after evaluating symptoms like reduced bowel movement frequency type or defecation difficulty type. The first line of treatment includes the improvement of lifestyle habits and diet therapy. The first drugs to consider for oral treatment are osmotic laxatives. If these are ineffective, secretagogues and ileal bile acid transporter inhibitors are candidates. However, stimulant laxatives are exclusively designated for as-needed use. Probiotics, bulk-forming laxatives, prokinetics, and Kampo medicines, for which there is insufficient evidence, are considered alternative or complementary therapy. Providing the best clinical strategies for chronic constipation therapy in Japan, these clinical guidelines for chronic constipation 2023 should prove useful for its treatment worldwide. The Japan Gastroenterological Association published the first version of its clinical guidelines for chronic constipation 2023. Based on the latest evidence, these guidelines describe the definition, classification, diagnostic criteria, diagnostic testing methods, epidemiology, pathophysiology, and treatment of chronic constipation. They include flowcharts for both diagnosis and treatment of chronic constipation. In the treatment of chronic constipation, the first step involves differentiating between secondary forms, such as organic disease-associated constipation, systemic disease-associated constipation, and drug-induced constipation. The next step is to determine whether the chronic constipation stems from a motility disorder, a form of primary chronic constipation. For functional constipation and constipation-predominant irritable bowel syndrome, treatment should be initiated after evaluating symptoms like reduced bowel movement frequency type or defecation difficulty type. The first line of treatment includes the improvement of lifestyle habits and diet therapy. The first drugs to consider for oral treatment are osmotic laxatives. If these are ineffective, secretagogues and ileal bile acid transporter inhibitors are candidates. However, stimulant laxatives are exclusively designated for","PeriodicalId":11315,"journal":{"name":"Digestion","volume":" ","pages":"62-89"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11825134/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142003881","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":"C-Kit Immunohistochemical Expression as a Complementary Method to Assess Mast Cell Density in Helicobacter pylori-Mediated Gastritis.","authors":"Ava T Ismael, Rafal A Abdulhameed, Bushra A Hamdi, Rawaz D Tawfeeq, Aram Ommar","doi":"10.1159/000541387","DOIUrl":"10.1159/000541387","url":null,"abstract":"<p><strong>Introduction: </strong>Chronic gastritis is a group of conditions commonly characterized by stomach lining inflammation. The study aimed to investigate the clinical and pathological aspects that play a role in its development. Additionally, the study examines the use of CD117 as an immunohistochemistry marker in evaluating mast cell density (MCD).</p><p><strong>Methods: </strong>This retrospective, cross-sectional study was conducted in Iraqi Kurdistan with a sample size of 380 patients. Patient data included gastritis type, neutrophil infiltration severity, mononuclear cell infiltration within the lamina propria, intestinal metaplasia, and glandular atrophy, which were categorized and given a score. The CD117 level was identified using an anti-human rabbit polyclonal antibody.</p><p><strong>Results: </strong>A statistically significant association was revealed between Helicobacter pylori-mediated gastritis and non-specific gastritis with age, activity, H. pylori and MCD, dysplasia, and malignancy. Meanwhile, no association was found with gender, inflammatory infiltrate, intestinal metaplasia, and glandular atrophy. C-Kit exhibited a marked increase in MCD in patients with H. pylori-mediated gastritis, intestinal metaplasia, atrophy, and gastric carcinoma. However, a significant decrease in MCD was observed on repeating endoscopy evaluations for patients after treatment.</p><p><strong>Conclusion: </strong>Regions that exhibit severe inflammation, metaplasia, atrophy, and carcinoma demonstrated an increase in MCD with H. pylori-mediated gastritis. A detailed investigation in clinical practice to screen early diagnosis and treatment needs to be performed in high H. pylori prevalence.</p>","PeriodicalId":11315,"journal":{"name":"Digestion","volume":" ","pages":"23-29"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282035","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":"NEIL3 Upregulated by TFAP2A Promotes M2 Polarization of Macrophages in Liver Cancer via the Mediation of Glutamine Metabolism.","authors":"Fabiao Zhang, Binfeng Wang, Wenlong Zhang, Yongfu Xu, Caiming Zhang, Xiangyang Xue","doi":"10.1159/000540804","DOIUrl":"10.1159/000540804","url":null,"abstract":"<p><strong>Introduction: </strong>Tumor-associated macrophages, which are part of the tumor microenvironment, are a major factor in cancer progression. However, a complete understanding of the regulatory mechanism of M2 polarization of macrophages (Mø) in liver cancer is yet to be established. This study aimed to investigate the potential mechanism by which NEIL3 influenced M2 Mø polarization in liver cancer.</p><p><strong>Methods: </strong>Bioinformatics analysis analyzed NEIL3 expression and its enriched pathways in liver cancer tissue, as well as its correlation with pathway genes. The upstream transcription factor of NEIL3, TFAP2A, was predicted and its expression in liver cancer tissue was analyzed. The binding relationship between the two was analyzed by dual-luciferase reporter and chromatin immunoprecipitation experiments. qRT-PCR assessed NEIL3 and TFAP2A levels in liver cancer cells. Cell viability was detected by CCK-8, while CD206 and CD86 expression was detected by immunofluorescence. IL-10 and CCR2 expressions were assessed using qRT-PCR, and M2 Mø quantity was detected using flow cytometry. Reagent kits tested glutamine (Gln) consumption, α-ketoglutarate, and glutamate content, as well as NADPH/NADP+ and GSH/GSSG ratios. Expression of Gln transport proteins was detected using Western blot. An animal model was established to investigate the influence of NEIL3 expression on liver cancer growth.</p><p><strong>Results: </strong>NEIL3 was highly expressed in liver cancer and promoted Mø M2 polarization through Gln metabolism. TFAP2A was identified as the upstream transcription factor of NEIL3 and was highly expressed in liver cancer. Rescue experiments presented that overexpression of NEIL3 reversed the suppressive effect of TFAP2A knockdown on Mø M2 polarization in liver cancer. In vivo experiments demonstrated that the knockdown of NEIL3 could significantly repress the growth of xenograft tumors.</p><p><strong>Conclusion: </strong>This study suggested that the TFAP2A/NEIL3 axis promoted Mø M2 polarization through Gln metabolism, providing a theoretical basis for immune therapy targeting the liver cancer TME.</p>","PeriodicalId":11315,"journal":{"name":"Digestion","volume":" ","pages":"30-44"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343593","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":"Clinical Efficacy and Safety of Treatments for Exocrine Pancreatic Insufficiency: A Systematic Literature Review.","authors":"Paula Chu, Jasmina Mioc, Peter O'Donovan, Owen Henry","doi":"10.1159/000541326","DOIUrl":"10.1159/000541326","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Exocrine pancreatic insufficiency (EPI) is caused by multiple clinical conditions such as cystic fibrosis and chronic pancreatitis (CP). Standard management of EPI includes pancreatic enzyme replacement therapy (PERT) along with consultation with a dietitian. While PERTs have been on the market for several decades, newer publications on their clinical efficacy and safety raised the need for a comprehensive review of the literature. We aimed to identify the available evidence on the clinical efficacy and safety of treatments for EPI to understand the current treatment landscape and unmet need in patients with EPI.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A systematic literature review (SLR) was conducted in Embase, Medline, and Evidence-Based Medicine databases from 2010 to 2022; conference proceedings from 2020 to 2022 were also searched. Articles were screened independently by two reviewers at abstract and full-text stage against predefined eligibility criteria.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;We identified 26 journal publications and two conference abstracts, reporting on 22 randomized control trials, four observational studies, and two single-arm interventional studies. The most reported treatment was pancrelipase, specifically Creon® (n = 12). Fourteen studies reported coefficient of fat absorption (CFA) results. Across studies, patients experienced a considerable increase in CFA post-initiation of treatment regardless of intervention or timepoint. Mean change in CFA ranged from 7.5% in patients with CP who received placebo to 36% in patients with CP treated with Creon®. Ten studies reported coefficient of nitrogen absorption (CNA). Where reported, pancrelipase (including Creon®) increased CNA levels in EPI patients compared to placebo. Only one study compared PERT brands head-to-head: no significant differences were reported in the CNA-72 h values (Creon® 82.0% [SE: 1.2] vs. Zenpep® 80.9% [SE: 1.2]). Loss of body weight and low body mass index (BMI) are important features of EPI. Overall, treatment with PERT increased BMI and body weight, or limited their decline, with increases ranging from 0.1 to 6.1 kg. Based on the 18 studies that reported safety outcomes, PERT was considered safe and well tolerated.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;This SLR confirmed that PERT is an effective and tolerable treatment option for patients with EPI. However, nutritional parameters and health-related quality of life data were sparsely reported, and future clinical trials should look to incorporate these data given their importance in clinical practice and patient outcomes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Exocrine pancreatic insufficiency (EPI) is caused by multiple clinical conditions such as cystic fibrosis and chronic pancreatitis (CP). Standard management of EPI includes pancreatic enzyme replacement therapy (PERT) along with consultation with a dietitian. While PERTs have been on the market for several decades, newer publ","PeriodicalId":11315,"journal":{"name":"Digestion","volume":" ","pages":"45-61"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11825132/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282036","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}