Digestive Diseases and Sciences最新文献

{"title":"CRYAB Promotes Colorectal Cancer Progression by Inhibiting Ferroptosis Through Blocking TRIM55-Mediated β-Catenin Ubiquitination and Degradation.","authors":"Haiyan Xia, Jingwen Chen, Wenbo Zhang, Ying Xu, Yongjun Nai, Xiaowei Wei","doi":"10.1007/s10620-024-08584-6","DOIUrl":"10.1007/s10620-024-08584-6","url":null,"abstract":"<p><strong>Background: </strong>α-Crystallin B (CRYAB) is a chaperone member of the HSPs family that protects proteins with which it interacts from degradation. This study aims to investigate the effect of CRYAB on the progression of colorectal cancer (CRC) and its underlying mechanism.</p><p><strong>Methods: </strong>CRYAB expression was evaluated in CRC tissues. Cell growth was tested by CCK-8 kit. Lipid reactive oxygen species (ROS) assays, lipid peroxidation assays, glutathione assays were used to assess the degree of cellular lipid peroxidation of CRC cells. The potential signal pathways of CRYAB were analyzed and verified by Western blot (WB) and immunoprecipitation (Co-IP).</p><p><strong>Results: </strong>CRYAB expression was elevated in CRC tissues and exhibited sensitivity and specificity in predicting CRC. Functionally, knockdown of CRYAB induced ferroptosis in CRC cells. Mechanistically, CRYAB binding prevented from β-catenin interacting with TRIM55, leading to an increase in β-catenin protein stability, which desensitized CRC cells to ferroptosis and ultimately accelerated cancer progression.</p><p><strong>Conclusions: </strong>Targeting CRYAB might be a promising strategy to enhance ferroptosis and improve the efficacy of CRC therapy.</p>","PeriodicalId":11378,"journal":{"name":"Digestive Diseases and Sciences","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11489300/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141912258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gastrocolonic Fistula Caused by Buckyballs.","authors":"Yi Chen, Bingqian Ni, Ningning You, Jinshun Zhang","doi":"10.1007/s10620-024-08608-1","DOIUrl":"10.1007/s10620-024-08608-1","url":null,"abstract":"","PeriodicalId":11378,"journal":{"name":"Digestive Diseases and Sciences","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An 'Adaptive Treatment Strategy' for Oral Vancomycin in Patients with the Orphan Disease Primary Sclerosing Cholangitis.","authors":"Ayesha Shah, James Tabibian, Cynthia Buness, Gerald J Holtmann","doi":"10.1007/s10620-024-08497-4","DOIUrl":"10.1007/s10620-024-08497-4","url":null,"abstract":"<p><p>Decision-making in clinical medicine ideally is based upon evidence from randomized, placebo-controlled trials (RCTs) and subsequent systematic reviews and meta-analyses. However, for orphan diseases, the expectation of having one or multiple RCTs that inform clinical guidelines or justify specific treatments can be unrealistic and subsequent therapeutic nihilism can be detrimental to patients. This article discusses the benefits of therapeutic decision-making in the context of orphan diseases, focusing on primary sclerosing cholangitis (PSC) as an example of an orphan disease with poor clinical outcomes. PSC is a rare disorder characterized by inflammation and progressive fibrosis of the bile ducts. It carries a high risk of liver failure, malignancies, and debilitating symptoms that impair quality of life. Liver transplantation is currently the only life-prolonging intervention for PSC, but it is not a curative option. The article highlights the potential benefits of treating PSC patients with oral vancomycin (OV), which has shown significant clinical responses and improved quality of life in some cases. However, access to OV therapy is limited due to the lack of RCTs supporting its use. The standard requirement of having evidence from RCTs may result in withholding potentially life-altering and/or life-saving treatments for patients with orphan diseases. Conducting RCTs is challenging in these patient populations due to difficulties in recruiting the required patient cohorts and limited commercial returns. A standardized 'adaptive treatment strategy' is proposed to address this. This approach leverages the best available evidence for specific treatments, considers individual clinical responses, and adjusts treatment over time.</p>","PeriodicalId":11378,"journal":{"name":"Digestive Diseases and Sciences","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11489242/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141418313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Odynophagia and Retrosternal Pain Are Common in Eosinophilic Esophagitis and Associated with an Increased Overall Symptom Severity.","authors":"Jeanine Karpf, Ekaterina Safroneeva, Jean-Benoit Rossel, Florian Hildenbrand, Catherine Saner, Thomas Greuter, Gerhard Rogler, Alex Straumann, Alain Schoepfer, Luc Biedermann, Fritz R Murray, Philipp Schreiner","doi":"10.1007/s10620-024-08586-4","DOIUrl":"10.1007/s10620-024-08586-4","url":null,"abstract":"<p><strong>Background and aims: </strong>Dysphagia is the hallmark symptom in eosinophilic esophagitis (EoE). However, data are limited regarding the overall prevalence and potential implications of atypical symptoms like odynophagia and retrosternal pain.</p><p><strong>Methods: </strong>Patients enrolled into the Swiss EoE cohort study (SEECS) were analyzed regarding the presence of odynophagia and retrosternal pain. Demographics, other EoE-related symptoms, histologic and endoscopic activity were compared between EoE-patients with vs. without odynophagia and/or retrosternal pain.</p><p><strong>Results: </strong>474 patients (75.2% male) were analyzed. In their individual course of disease 110 (23.2%) patients stated to have ever experienced odynophagia and 64 (13.5%) retrosternal pain independent of food intake, 24 (5%) patients complained about both symptoms. Patients with odynophagia consistently scored higher in symptom severity (p < 0.001), EREFS score (median 3.0 vs. 2.0, p = 0.006), histologic activity and a lower quality of life (p = 0.001) compared to patients without odynophagia. Sex, age at diagnosis, EoE-specific treatment, complications such as candida or viral esophagitis and disease duration were similar in patients with vs. without odynophagia. Also patients with retrosternal pain scored higher in symptom severity (2.0 vs. 1.0, p = 0.001 and 2.0 vs. 1.0, p < 0.001 in physician and patient questionnaire assessment, respectively). However, there was neither a difference in endoscopic/histologic disease activity nor in quality of life according to presence or absence of retrosternal pain. Due to logistic reasons, a stratification regarding the presence of concomitant dysphagia was not possible.</p><p><strong>Conclusion: </strong>Odynophagia and swallowing-independent retrosternal pain are common symptoms in patients with EoE, associate with an overall higher EoE-related symptom severity and for the case of odynophagia lower quality of life. However, the influence of concomitant dysphagia and its severity remains unclear and needs to be included in future analyses.</p>","PeriodicalId":11378,"journal":{"name":"Digestive Diseases and Sciences","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11489245/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protein-Losing Enteropathy Combined with Multiple Gastrointestinal Venous Ectasia.","authors":"Siyuan Chen, Yihao Wu, Ziru Zhou, Jing Sun, Qiang Zhan","doi":"10.1007/s10620-024-08605-4","DOIUrl":"10.1007/s10620-024-08605-4","url":null,"abstract":"","PeriodicalId":11378,"journal":{"name":"Digestive Diseases and Sciences","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Xanthogranulomatous Pancreatitis Showing Morphologic Overlap with Type 1 Autoimmune Pancreatitis.","authors":"Chika Iguh, David Sin, Caroline Yap","doi":"10.1007/s10620-024-08614-3","DOIUrl":"10.1007/s10620-024-08614-3","url":null,"abstract":"","PeriodicalId":11378,"journal":{"name":"Digestive Diseases and Sciences","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Incidence of Post-ERCP Pancreatitis in Patients Receiving Rectal Indomethacin vs. Compounded Rectal Diclofenac Prophylaxis.","authors":"Laurens P Janssens, Aishwarya Yamparala, John Martin, John O'Meara, William S Harmsen, Thanmay Sathi, Elizabeth Lemke, Barham K Abu Dayyeh, Aliana Bofill-Garcia, Bret T Petersen, Andrew C Storm, Mark Topazian, Eric J Vargas, Vinay Chandrasekhara, Ryan J Law","doi":"10.1007/s10620-024-08604-5","DOIUrl":"10.1007/s10620-024-08604-5","url":null,"abstract":"<p><strong>Background and aims: </strong>Endoscopic retrograde cholangiopancreatography (ERCP) carries a 3-15% risk of post-ERCP pancreatitis (PEP). Rectal indomethacin reduces the risk of PEP, but its cost has increased more than 20-fold over the past decade. Rectal diclofenac is also used to prevent PEP but is not commercially available in the United States. The aim of this study is to compare the incidence of PEP after administration of commercially available rectal indomethacin versus compounded rectal diclofenac and assess financial implications.</p><p><strong>Methods: </strong>ERCP cases at our institution with administration of 100 mg rectal indomethacin or 100 mg compounded rectal diclofenac between May 2018 and January 2022 were retrospectively reviewed. The incidence and severity of PEP was compared between the indomethacin (n = 728) and diclofenac (n = 304) groups. Risk factors (young age, female sex, history of pancreatitis or PEP, sphincterotomy during procedure, pancreatic indication, trainee involvement) and protective factors (prior sphincterotomy, pancreatic duct stenting) for PEP were compared between groups.</p><p><strong>Results: </strong>60 patients (8.2%) in the rectal indomethacin group and 25 patients (8.2%) in the compounded rectal diclofenac group developed PEP, resulting in moderate or severe PEP in 9 (15.0%) and 2 (8.0%) patients, respectively. The compounded rectal diclofenac group had more trainee involvement (46.1% vs. 32.8%, p = 0.0001) and more prior sphincterotomy cases (15.8% vs. 10.6%, p = 0.0193) compared to the rectal indomethacin group; no statistically significant differences were observed in all other risk and protective factors. Following switch to compounded rectal diclofenac, institutional annual cost savings amounted to $441,460.62 and patient charge decreased 45-fold.</p><p><strong>Conclusion: </strong>This retrospective single-center real-world analysis showed similar efficacy of rectal indomethacin and compounded rectal diclofenac in preventing PEP but demonstrates substantial cost savings after switching to compounded rectal diclofenac.</p>","PeriodicalId":11378,"journal":{"name":"Digestive Diseases and Sciences","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Does Gastroesophageal Reflux Disease Increase the Risk of Sepsis and Its 28-day Mortality? A Causal Study Using a Mendelian Randomization Approach.","authors":"Runquan Zhou, Wenjuan Li, Fan Wu, Yuanhui Sheng, Shan Xu, Yi Liu, Dan Zhang, Mingxing Wang","doi":"10.1007/s10620-024-08625-0","DOIUrl":"10.1007/s10620-024-08625-0","url":null,"abstract":"<p><strong>Background: </strong>Gastroesophageal reflux disease (GERD) is a prevalent gastrointestinal disorder. Recent studies indicate that GERD may exert systemic effects, potentially elevating the risk of severe infections, including sepsis. Nevertheless, the causal relationship between GERD and sepsis, as well as sepsis-related 28-day mortality, remains uncertain.</p><p><strong>Aim: </strong>The aim of this study is to investigate the causal relationship between GERD and the risk of sepsis, including 28-day mortality of sepsis.</p><p><strong>Methods: </strong>This study utilized a two-sample Mendelian Randomization (MR) approach to analyze data from publicly available genome-wide association studies (GWAS) databases ( https://gwas.mrcieu.ac.uk/ ). The analysis comprised 129,080 cases and 473,524 controls for GERD; 11,643 patients and 474,841 controls for sepsis; and 1,896 patients and 484,588 controls for 28-day mortality from sepsis. The objective was to evaluate the causal impact of GERD on the risk of sepsis and 28-day sepsis mortality. Genetic variation data pertinent to GERD were obtained from the most recent genome-wide association studies (GWAS). The primary analysis employed the Inverse Variance Weighted (IVW) method. Sensitivity and pleiotropy analyses were performed to validate the robustness of the findings.</p><p><strong>Results: </strong>MR analysis revealed a notable link between genetically predicted GERD and increased sepsis risk (odds ratio [OR] 1.37, 95% confidence interval [CI] 1.24-1.52; p = 2.79 × 10-9). Moreover, GERD correlated with elevated 28-day mortality of sepsis (OR 1.44, 95% CI 1.11-1.85; p = 5.34 × 10-3). These results remained consistent throughout various sensitivity analyses, indicating their resilience against potential pleiotropy and other biases.</p><p><strong>Conclusion: </strong>This study indicates that genetic predisposition to GERD may be linked to an elevated risk of sepsis and its associated 28-day mortality. However, the study does not establish a direct causal relationship for GERD itself, nor does it assess the impact of GERD treatment. Further research is needed to explore the underlying mechanisms and potential therapeutic interventions involved.</p>","PeriodicalId":11378,"journal":{"name":"Digestive Diseases and Sciences","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142125148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low-Grade Activation of the Extrinsic Coagulation Pathway in Patients with Ulcerative Colitis.","authors":"Ioannis Drygiannakis, Vassilis Valatas, Eirini Filidou, Niki Tzenaki, Evangelia Archontoulaki, Nikolas Dovrolis, Leonidas Kandilogiannakis, Georgios Kefalogiannis, Prodromos Sidiropoulos, George Kolios, Ioannis E Koutroubakis","doi":"10.1007/s10620-024-08640-1","DOIUrl":"10.1007/s10620-024-08640-1","url":null,"abstract":"<p><strong>Background: </strong>Ulcerative colitis (UC) increases the risk for venous thromboembolism. Tissue factor (TF) initiates the extrinsic coagulation pathway (ECP).</p><p><strong>Aims: </strong>To investigate the correlation of UC severity with latent ECP activation and TF expression in primary colonic stromal cells (PCSC).</p><p><strong>Methods: </strong>In plasma of 38 UC patients (31 males, disease duration 151 ± 25 months) and 28 healthy controls, exosomes and microparticles (EM) were counted. Moreover, TF protein concentration, activities of EM-bound TF (EM-TFa) and coagulation factor VII (FVIIa) were assessed. In PCSC in culture, TF mRNA (F3) from 12 patients with active UC and 7 controls was evaluated.</p><p><strong>Results: </strong>UC patients had 4- and 3.7- times more exosomes and microparticles, respectively, than controls. TF protein in UC was correlated with several disease severity indices, such as partial Mayo score (pMs; r 0.443), albumin (- 0.362), ESR (0.353), PLT (0.575), and endoscopic Ms (eMs 0.468). EM-TFa was also significantly higher in UC and was correlated to SIBDQ (- 0.64), albumin (- 0.624), disease extent and eMs (0.422). Refractory-to-treatment patients had significantly higher TF protein, EM-TFa and FVIIa. Even within responders, the need for steroids or biologics correlated with a 2.2-times higher EM-TFa. PCSC from active UC maintained higher F3 than controls, which was correlated to pMs (0.56), albumin (- 0.543) and eMs. Treatment with cytokines further upregulated F3. P for all comparisons was < 0.05.</p><p><strong>Conclusion: </strong>Low-grade activation of the ECP associates with clinical, endoscopic UC activity and response to treatment. TF in PCSC mirrors its systemic activity and points to them as a source.</p>","PeriodicalId":11378,"journal":{"name":"Digestive Diseases and Sciences","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ZIP8 A391T Crohn's Disease-Linked Risk Variant Induces Colonic Metal Ion Dyshomeostasis, Microbiome Compositional Shifts, and Inflammation.","authors":"Julianne C Yang, Matthew Zhao, Diana Chernikova, Nerea Arias-Jayo, Yi Zhou, Jamilla Situ, Arjun Gutta, Candace Chang, Fengting Liang, Venu Lagishetty, Jonathan P Jacobs","doi":"10.1007/s10620-024-08647-8","DOIUrl":"10.1007/s10620-024-08647-8","url":null,"abstract":"<p><strong>Background: </strong>The pathogenesis of Crohn's disease involves genetic and environmental factors, with the gut microbiome playing a crucial role. The Crohn's disease-associated variant rs13107325 in the SLC39A8 gene results in an A391T substitution in the ZIP8 metal ion transporter and has previously been linked to alterations in the colonic microbiome in variant carriers. We hypothesized that the A391T substitution alters metal ion homeostasis in the colonic mucosal-luminal interface, thereby inducing dysbiosis which may promote intestinal inflammation.</p><p><strong>Methods: </strong>To evaluate this hypothesis, we generated a SLC39A8 A393T mouse model (matching human A391T). We first examined trace element abundance in the colonic mucosal epithelium and lumen of homozygous A393T and wild-type (WT) mice to determine if the variant affected metal distribution. We also performed 16S rRNA gene sequencing on colon samples at 2 months, 3-4 months, and 12 months of age, and conducted histological scoring of colon tissue collected from 5-month and 10-month old mice.</p><p><strong>Results: </strong>Consistent with an effect of the variant on ZIP8 function, homozygous A393T mice exhibited increased cobalt in the colonic mucosa, but reduced iron, zinc, manganese, cobalt, copper, and cadmium in the colonic lumen. 16S rRNA gene sequencing of colon samples revealed variant-linked effects on microbiome beta diversity in 2-month-, 3-4-month-, and 12-month-old mice. Histological scoring showed spontaneous intestinal inflammation in 10-month but not in 5-month-old mice. Lastly, predicted pathway analysis of the microbiome samples revealed differential enrichment of iron-, zinc-, and cobalt-dependent pathways in A393T mice compared to wild-type controls.</p><p><strong>Conclusion: </strong>These results suggest that the variant in SLC39A8 primarily restricts metal availability to the microbiota, resulting in compositions that can adapt to the environment and that A393T-linked dysbiosis occurs prior to the onset of inflammation. This study paves the way for future studies investigating risk variants as microbiome-disease modifiers.</p>","PeriodicalId":11378,"journal":{"name":"Digestive Diseases and Sciences","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11489278/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}