Article
Gastroenterology & Hepatology
James J. Ashton, Eleanor G. Seaby, R. Mark Beattie, Sarah Ennis
Summary: Studies have shown that NOD2 is the most important gene in the pathogenesis of Crohn's disease, but its complexity remains unresolved. Recent research has suggested that NOD2 may be a single-gene cause of the disease, and the specific phenotype associated with NOD2-related disease offers opportunities for personalized diagnosis, disease prediction, and targeted therapy. However, there are still many unknowns about the genomics of NOD2 that require further investigation.
JOURNAL OF CROHNS & COLITIS
(2023)
Review
Biochemistry & Molecular Biology
Aiko Robert, Michael Scholl, Thomas Vogels
Summary: Recent research has shown that injecting purified tau aggregates from human tauopathy patients can replicate the structural features and cell type specificity of the original tau pathology. These models may have unique translational value in studying the functional consequences of tau pathology, tau-based diagnostics, and tau-targeting therapeutics.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Medicine, General & Internal
Marta Kaczmarek-Rys, Szymon Tytus Hryhorowicz, Emilia Lis, Tomasz Banasiewicz, Jacek Paszkowski, Maciej Borejsza-Wysocki, Jaroslaw Walkowiak, Wojciech Cichy, Piotr Krokowicz, Elzbieta Czkwianianc, Andrzej Hnatyszyn, Iwona Krela-Kazmierczak, Agnieszka Dobrowolska, Ryszard Slomski, Andrzej Plawski
Summary: This study investigated the relationship between NOD2 gene haplotypes and the occurrence, clinical presentation, and onset of inflammatory bowel disease (IBD). Certain haplotypes were found to be associated with specific clinical characteristics of IBD, such as the late-onset form of Crohn disease (CD) and CD in children. The presence of specific alleles within haplotypes may play a fundamental role in the development of IBD.
JOURNAL OF CLINICAL MEDICINE
(2021)
Review
Medicine, Research & Experimental
Shuangshuang Lu, Keyuan Zhu, Yongxin Guo, Enjing Wang, Jin Huang
Summary: This review summarized the characteristics and experimental methods of commonly used animal models of CD with anal fistula, pointing out the necessity of establishing a suitable animal preclinical model.
EXPERIMENTAL AND THERAPEUTIC MEDICINE
(2021)
Review
Biochemistry & Molecular Biology
Danielle Kamato, Iqra Ilyas, Suowen Xu, Peter J. Little
Summary: Cardiovascular disease, primarily caused by atherosclerosis, is the leading cause of disease-related mortality worldwide. Current therapeutic agents have limited efficacy in lowering plasma lipid levels and reducing deaths from cardiovascular disease. Suitable animal models that accurately reproduce human atherosclerosis are essential for pre-clinical research on novel cardiovascular drugs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Gastroenterology & Hepatology
James J. Ashton, Guo Cheng, Imogen S. Stafford, Melina Kellermann, Eleanor G. Seaby, J. R. Fraser Cummings, Tracy A. F. Coelho, Akshay Batra, Nadeem A. Afzal, R. Mark Beattie, Sarah Ennis
Summary: CD is highly heterogenous and may have stricturing behavior. A NOD2 genomic biomarker can predict stricturing risk, with prognostic power improved in pediatric-onset CD. Implementation into clinical setting can help personalize management.
INFLAMMATORY BOWEL DISEASES
(2023)
Article
Biochemistry & Molecular Biology
Tae Hoon Kim, Nayoung Bae, Taeho Kim, Albert L. Hsu, Mark Hunter, Jung-Ho Shin, Jae-Wook Jeong
Summary: Endometriosis is positively associated with obesity, but negatively associated with low BMI. High-fat diet-induced obesity can increase the development of endometriosis, while obesity with leptin deficiency and leptin receptor deficiency can suppress the development of endometriosis. These findings suggest that leptin and its receptor play a critical role in the development of endometriosis.
Article
Multidisciplinary Sciences
Julie E. Horowitz, Neil Warner, Jeffrey Staples, Eileen Crowley, Nehal Gosalia, Ryan Murchie, Cristopher Van Hout, Karoline Fiedler, Gabriel Welch, Alejandra Klauer King, Jeffrey G. Reid, John D. Overton, Aris Baras, Alan R. Shuldiner, Anne Griffiths, Omri Gottesman, Aleixo M. Muise, Claudia Gonzaga-Jauregui
Summary: Inflammatory bowel disease (IBD) is a chronic inflammation of the gastrointestinal tract, including Crohn's disease (CD), ulcerative colitis (UC), or IBD-unclassified. Approximately 25% of all IBD diagnoses are pediatric onset, with 8% potentially influenced by biallelic rare NOD2 variants. Recessive inheritance of NOD2 alleles may be a mechanistic driver of early onset IBD.
SCIENTIFIC REPORTS
(2021)
Editorial Material
Microbiology
Xiaolong He, Hongwei Zhou
Summary: In this study, Jang et al. reveal a paradoxical relationship between excessive REG3 expression and depletion of protective enterococci in IBD patients. This depletion impairs the anti-inflammatory pathway and perpetuates inflammation, providing insight into the pathogenesis of IBD.
CELL HOST & MICROBE
(2023)
Article
Multidisciplinary Sciences
Shikha Nayar, Joshua K. Morrison, Mamta Giri, Kyle Gettler, Ling-Shiang Chuang, Laura A. Walker, Huaibin M. Ko, Ephraim Kenigsberg, Subra Kugathasan, Miriam Merad, Jaime Chu, Judy H. Cho
Summary: NOD2 deficiency contributes to fibrosis and stricturing complications in Crohn's disease through dysregulated homeostasis of activated fibroblasts and macrophages, which can be ameliorated by gp130 blockade. Carriers of NOD2 risk alleles exhibit dysregulated homeostasis of activated fibroblasts and macrophages, suggesting a potential role for gp130 blockade in rescuing the activated program caused by NOD2 mutations.
Article
Microbiology
Jie Gao, Xinmei Zhao, Shixian Hu, Zhenhe Huang, Mengyao Hu, Shaoqin Jin, Bingyun Lu, Kai Sun, Zhang Wang, Jingyuan Fu, Rinse K. Weersma, Xiaolong He, Hongwei Zhou
Summary: This study reveals that the depletion of DL-endopeptidase contributes to the pathogenesis of Crohn's disease through NOD2 signaling, providing a potential therapeutic target.
CELL HOST & MICROBE
(2022)
Review
Immunology
Yinxi Zhou, Jinghua Xia, Shuonan Xu, Tao She, Yanning Zhang, Ying Sun, Miaomiao Wen, Tao Jiang, Yanlu Xiong, Jie Lei
Summary: The development and growth of tumors pose a significant and ongoing threat to human life globally. Despite the remarkable progress achieved by advanced therapeutic strategies such as immune checkpoint therapy and CAR-T in treating solid and hematological malignancies, the malignant initiation and progression of cancer remains controversial and requires further research. Experimental animal models not only have great advantages in simulating tumor occurrence, development, and malignant transformation mechanisms, but also can be used to evaluate the therapeutic effects of diverse clinical interventions, gradually becoming indispensable in cancer research. This paper reviews recent research progress in mouse and rat models, focusing on spontaneous, induced, transgenic, and transplantable tumor models, aiming to provide guidance for future studies on malignant mechanisms and tumor prevention.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Pharmacology & Pharmacy
Snjezana Cuzic, Maja Antolic, Anja Ognjenovic, Darija Stupin-Polancec, Adriana Petrinic Grba, Boska Hrvacic, Miroslava Dominis Kramaric, Sanja Musladin, Lidija Pozgaj, Ivo Zlatar, Denis Polancec, Gorana Aralica, Marko Banic, Marija Urek, Brankica Mijandrusic Sincic, Aleksandar Cubranic, Ines Glojnaric, Martina Bosnar, Vesna Erakovic Haber
Summary: This study explored the expression of claudins in human disease and two different animal models of IBD. The diverse alterations in claudin expression by epithelial and inflammatory cells were recorded in IBD and both animal models. The results suggest that claudins are not exclusively expressed by epithelial cells, and changes in claudin mRNA levels should be interpreted in the context of overall tissue alterations.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Multidisciplinary Sciences
Nicolas Rochereau, Xavier Roblin, Eva Michaud, Remi Gayet, Blandine Chanut, Fabienne Jospin, Blaise Corthesy, Stephane Paul
Summary: In this study, it was found that NOD2 mutation increases the transport of SIgA in the gut, potentially impacting gut inflammation by altering gut microfold cells.
NATURE COMMUNICATIONS
(2021)
Article
Immunology
Liming Mao, Atika Dhar, Guangxun Meng, Ivan Fuss, Kim Montgomery-Recht, Zhiqiong Yang, Qiuyun Xu, Atsushi Kitani, Warren Strober
Summary: These studies provide insights into the pathogenesis of Blau syndrome and the role of NOD2 gene mutations. The findings suggest that Blau NOD2 mutations lead to loss of NOD2 signaling and disruption of NOD2-mediated cross-regulation, resulting in inflammation. The studies also indicate that NOD2-mediated cross-regulation is controlled by IRF4, and faulty NOD2 signaling reduces IRF4 expression and contributes to inflammation.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Pediatrics
Nathan S. Rubalcava, Natalie A. Moreno, Jeremy Adler, James D. Geiger, Ronald B. Hirschl, Samir K. Gadepalli
Summary: The study compared the outcomes of two-stage operations with different timing of pouch creation, showing that delaying pouch creation to the second operation without a protective ileostomy is safe for a sicker and more acute pediatric population.
JOURNAL OF PEDIATRIC SURGERY
(2021)
Editorial Material
Gastroenterology & Hepatology
Jeremy Adler, Grace J. Lee, Andrew A. M. Singer
INFLAMMATORY BOWEL DISEASES
(2022)
Article
Gastroenterology & Hepatology
Lindsey S. Lawrence, Amer Heider, Andrew A. M. Singer, Haley C. Neef, Jeremy Adler
Summary: Granulomas are associated with an increased risk of perianal fistula but not with stricture in patients with Crohn's disease. Immune-modulating therapies and anti-TNF-alpha therapy were found to reduce the risk of both perianal fistula and stricture development. Patients with granulomatous inflammation were more responsive to anti-TNF therapy in terms of reducing the risk of perianal fistula compared to immunomodulators.
INFLAMMATORY BOWEL DISEASES
(2022)
Article
Gastroenterology & Hepatology
Prashanthi Kandavel, Sally J. Eder, Jeremy Adler
Summary: The study found that corticosteroid use among pediatric patients with inflammatory bowel disease in the ImproveCareNow Network has decreased over time. Racial disparities in corticosteroid use were noted, but gradually improved as corticosteroid use decreased. As corticosteroid use decreased, steroid-sparing therapy increased and there were improvements in height and weight z scores among children with Crohn disease.
JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION
(2021)
Article
Pediatrics
Nathan S. Rubalcava, Samir K. Gadepalli, Cory N. Criss, Natalie A. Moreno, Jeremy Adler, James D. Geiger
Summary: Surgical management for pediatric patients with UC can be done as either 1- or 2-stage operations, with similar short-term, long-term, and functional outcomes. 1-stage RP/IPAA operations without ileostomy are a safe alternative for patients considered for a 2-stage operation.
PEDIATRIC SURGERY INTERNATIONAL
(2021)
Article
Gastroenterology & Hepatology
Michael D. Kappelman, Kimberly N. Weaver, Xian Zhang, Xiangfeng Dai, Runa Watkins, Jeremy Adler, Marla C. Dubinsky, Arthur Kastl, Athos Bousvaros, Jenifer A. Strople, Raymond K. Cross, Peter D. R. Higgins, Ryan C. Ungaro, Meenakshi Bewtra, Emanuelle A. Bellaguarda, Francis A. Farraye, Margie E. Boccieri, A. Firestine, Kelly Y. Chun, Manory Fernando, Monique Bastidas, Michael Zikry, Millie D. Long
Summary: Although most patients with IBD show an initial response to SARS-CoV-2 vaccination, older patients and those treated with anti-TNF and immunomodulator have blunted responses and may benefit from an additional vaccine dose. Patients treated with other classes of immunosuppressive medications have more robust initial immune responses to vaccination.
AMERICAN JOURNAL OF GASTROENTEROLOGY
(2022)
Article
Gastroenterology & Hepatology
Jeremy Adler, Sally J. Eder, Acham Gebremariam, Christopher J. Moran, Lee M. Bass, Jonathan Moses, Jeffery D. Lewis, Andrew A. M. Singer, Tina L. Morhardt, Joseph A. Picoraro, Vanessa Cardenas, George M. Zacur, Richard B. Colletti
Summary: The study evaluated a simplified method for retrospectively assessing colonoscopy reports, finding that it accurately and reliably correlates with assessments from colonoscopy videos.
INFLAMMATORY BOWEL DISEASES
(2022)
Article
Gastroenterology & Hepatology
Kimberly N. Weaver, Xian Zhang, Xiangfeng Dai, Runa Watkins, Jeremy Adler, Marla C. Dubinsky, Arthur Kastl, Athos Bousvaros, Jennifer A. Strople, Raymond K. Cross, Peter D. R. Higgins, Ryan C. Ungaro, Meenakshi Bewtra, Emanuelle Bellaguarda, Francis A. Farraye, Margie E. Boccieri, Ann Firestine, Michael D. Kappelman, Millie D. Long
Summary: The severe acute respiratory syndrome coronavirus 2 vaccine is safe and well tolerated among individuals with inflammatory bowel disease (IBD) with low rates of adverse events and flare-ups.
INFLAMMATORY BOWEL DISEASES
(2022)
Article
Gastroenterology & Hepatology
Kimberly N. Weaver, Xian Zhang, Xiangfeng Dai, Wenli Chen, Runa Watkins, Jeremy Adler, Marla C. Dubinsky, Arthur Kastl, Athos Bousvaros, Jennifer A. Strople, Raymond K. Cross, Peter D. R. Higgins, Ryan C. Ungaro, Meenakshi Bewtra, Emanuelle Bellaguarda, Francis A. Farraye, Riley Craig, Cristian Hernandez, Margie E. Boccieri, Ann Firestine, Kelly Y. Chun, Millie D. Long, Michael D. Kappelman
Summary: In this study, we found low rates of breakthrough COVID-19 infection and mild illness in a large cohort of inflammatory bowel disease patients following vaccination with severe acute respiratory syndrome coronavirus 2. Residence in southern United States and lower median anti-receptor binding antibody level were associated with the development of COVID-19.
INFLAMMATORY BOWEL DISEASES
(2023)
Article
Gastroenterology & Hepatology
Arthur J. Kastl, Kimberly N. Weaver, Xian Zhang, Jennifer A. Strople, Jeremy Adler, Marla C. Dubinsky, Athos Bousvaros, Runa Watkins, Xiangfeng Dai, Wenli Chen, Raymond K. Cross, Peter D. R. Higgins, Ryan C. Ungaro, Meenakshi Bewtra, Emanuelle A. Bellaguarda, Francis A. Farraye, Kelly Y. Chun, Michael Zikry, Manory Fernando, Monique Bastidas, Cristian G. Hernandez, Riley G. Craig, Margie E. Boccieri, Anne Firestine, Millie D. Long, Michael D. Kappelman
Summary: Children with IBD show a robust immune response to COVID-19 vaccination with low adverse events, providing a high level of reassurance to the medical community and patients.
AMERICAN JOURNAL OF GASTROENTEROLOGY
(2023)
Article
Gastroenterology & Hepatology
Jeremy Adler, Richard B. Colletti, Lenore Noonan, Tyler M. Berzin, Adam S. Cheifetz, Laurie S. Conklin, Timothy C. Hoops, Christopher S. Huang, Blair Lewis, Daniel S. Mishkin, Kim Hung Lo, Yongling Xiao, Sheri Volger
Summary: The study found that SEMA-CD is reliable, reproducible, and sensitive to change, with a strong correlation to SES-CD. It was also rated easier to score by professionals compared to SES-CD.
INFLAMMATORY BOWEL DISEASES
(2023)
Article
Public, Environmental & Occupational Health
Joann M. Samalik, Caren S. Goldberg, Zubin J. Modi, Emily M. Fredericks, Samir K. Gadepalli, Sally J. Eder, Jeremy Adler
Summary: This study found that there are inaccuracies in the recording of race and ethnicity in the electronic health record (EHR), especially for patients who self-identify as minorities. This can result in under-representation of minorities in the EHR. Accurately recording race and ethnicity has important implications for disparity research and health policy.
JOURNAL OF RACIAL AND ETHNIC HEALTH DISPARITIES
(2022)
Article
Gastroenterology & Hepatology
Siddharth Singh, Ashwin N. Ananthakrishnan, Nghia H. Nguyen, Benjamin L. Cohen, Fernando S. Velayos, Jennifer M. Weiss, Shahnaz Sultan, Shazia M. Siddique, Jeremy Adler, Karen A. Chachu
Summary: This study provides conditional recommendations for the use of biomarkers in the management of ulcerative colitis (UC). The study suggests using biomarkers for monitoring during symptom remission and treatment decision making during moderate to severe symptoms. The study also highlights the optimal use and future research directions for biomarkers.
Meeting Abstract
Gastroenterology & Hepatology
Chun Chieh Lin, Samir Gadepalli, Jeremy Adler
AMERICAN JOURNAL OF GASTROENTEROLOGY
(2022)
Article
Gastroenterology & Hepatology
Andrew A. M. Singer, Annemarie Rompca, Samir K. Gadepalli, Jeremy Adler
Summary: The aim of this study was to determine predictors of perianal fistula healing among pediatric patients newly diagnosed with Crohn disease. Results showed that fistulotomy, fistulectomy, lesion removal, and non-White race were associated with delayed fistula healing. Treatment with anti-TNF alpha combined with therapeutic drug monitoring was associated with faster healing.
JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION
(2022)