Review
Pediatrics
Li-Na Wu, Zhi-Jun Zhu, Li-Ying Sun
Summary: Biliary Atresia is a common cause of neonatal cholestasis and a primary indication for Liver Transplantation. Genetic variants play a crucial role in the development of this condition. This review summarizes and analyzes the genetic variants of Biliary Atresia from a pathological perspective, providing a foundation for further research and treatment.
FRONTIERS IN PEDIATRICS
(2022)
Article
Gastroenterology & Hepatology
Guotao Wang, Huadong Chen, Panpan Sun, Wenying Zhou, Hong Jiang, Zhihai Zhong, Meixi Chen, Xiaoyan Xie, Zhenhua Luo, Luyao Zhou
Summary: This study aims to develop a comprehensive gene-clinical model based on two-dimensional shear wave elastography (2DSWE), liver gene expression, and other clinical parameters to predict response to Kasai portoenterostomy (KPE) surgery for infants with biliary atresia (BA). Using RNA sequencing analysis, differentially expressed gene patterns between BA and non-BA control samples were identified, and a nine-gene prognostic classifier was generated. A nomogram model based on the nine-gene classifier, age, preoperative 2DSWE, and albumin was constructed and validated, accurately predicting response to KPE for BA patients.
HEPATOLOGY RESEARCH
(2023)
Article
Pediatrics
Bo Wu, Ying Zhou, Xinbei Tian, Wei Cai, Yongtao Xiao
Summary: This study evaluated the diagnostic values of matrix metalloprotease-7 (MMP-7), interleukin-8 (IL-8), and gamma-glutamyl transferase (GGT) in children with biliary atresia (BA). The results showed that these biomarkers have good accuracy in differentiating BA from non-BA and diagnosing cholic stool in infants.
EUROPEAN JOURNAL OF PEDIATRICS
(2022)
Article
Multidisciplinary Sciences
Wison Laochareonsuk, Komwit Surachat, Piyawan Chiengkriwate, Surasak Sangkhathat
Summary: Cholestatic jaundice is a common neonatal condition, and biliary atresia (BA) is a correctable cholangiopathy. This study aimed to explore the pathogenesis of BA by studying genetic variations and found a correlation between different pathways of cholestatic diseases and BA.
Article
Gastroenterology & Hepatology
Sujit K. Mohanty, Bryan Donnelly, Haley Temple, Sarah Mowery, Holly M. Poling, Jaroslaw Meller, Astha Malik, Monica McNeal, Greg Tiao
Summary: Biliary atresia (BA) is a neonatal inflammatory bile duct disease that requires surgical intervention for biliary drainage restoration. Most diagnosed BA patients progress to end-stage liver disease even after successful surgery, necessitating liver transplantation. This study found that Hsc70 may serve as a therapeutic target for BA.
HEPATOLOGY COMMUNICATIONS
(2022)
Article
Gastroenterology & Hepatology
Iiris Nyholm, Maria Hukkinen, Marjut Pihlajoki, Joseph R. Davidson, Athanasios Tyraskis, Jouko Lohi, Paivi Heikkila, Satu Hanninen, Noora Andersson, Katja Eloranta, Olli Carpen, Markku Heikinheimo, Mark Davenport, Mikko P. Pakarinen
Summary: This study found that the expression of FGF19 in the liver was significantly increased in patients with biliary atresia, and the level of FGF19 in the serum was related to the surgical outcomes and liver histopathology. Low levels of serum FGF19 can predict the liver survival rate in patients with biliary atresia. In addition, serum FGF19 was positively correlated with the levels of primary bile acids and ductular reaction.
Article
Medicine, General & Internal
Yongliang Wang, Hongtao Yuan, Maojun Zhao, Li Fang
Summary: This study aimed to identify gene expression signature in biliary atresia (BA) using weighted gene co-expression network analysis. The results revealed a strong positive correlation between a specific gene module (brown module) and BA. Functional enrichment analysis showed that the module genes were involved in biological processes, metabolic pathways, and cell adhesion molecules. The combination of keratin 7 (KRT7) and C-X-C motif chemokine ligand 8 (CXCL8) was identified as a potential diagnostic model for BA.
Article
Pediatrics
Jiaxu Zhang, Yi Luo, Mingxuan Feng, Qiang Xia
Summary: Biliary atresia is strongly associated with immune response, with differentially expressed immune-related genes and cell types identified in the liver. Further correlation analysis suggests potential markers for fibrosis and inflammation in BA liver.
FRONTIERS IN PEDIATRICS
(2022)
Review
Immunology
Helen C. Su
Summary: Clinical observations and mechanistic studies in DOCK8-deficient patients and mice have uncovered multiple mechanisms contributing to their prevalent and severe allergic disease manifestations. Physical interactions of DOCK8 with STAT3 in B and T cells may lead to increased IgE isotype switching or defective immune synapse formation, resulting in weakened T-cell receptor signaling. The newly discovered TFH13 cell type, increased in DOCK8 deficiency, promotes life-threatening allergy through IL-13 production. Cytoskeletal derangements and cytothripsis can also lead to increased production of IL-4, IL-5, and IL-13 by myeloid cells and T cells, while impacts on type-2 innate lymphoid cells may contribute to allergic disease.
CURRENT OPINION IN IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
M. Zanjirband, R. Hodayi, Z. Safaeinejad, M. H. Nasr-Esfahani, R. Ghaedi-Heydari
Summary: This study investigated the impact of the p53 pathway in enhancing apoptosis and abnormal function of granulosa cells. Results suggest that p53 target genes play a critical role in the pathogenesis of PCOS, specifically through the enhancement of apoptosis in granulosa cells.
SCIENTIFIC REPORTS
(2023)
Article
Veterinary Sciences
Asmaa M. I. Abuzeid, Mahmoud M. Hefni, Yue Huang, Long He, Tingting Zhuang, Guoqing Li
Summary: This study identified and examined Prohemistomum vivax in experimentally infected pigeons, analyzing the histopathological lesions and cytokine expression. The findings revealed an early immunosuppressive state followed by a mixed Th1/Th2 immune response during the infection. Inflammatory cytokines were overexpressed, while regulatory T cell cytokines helped maintain immune homeostasis.
FRONTIERS IN VETERINARY SCIENCE
(2022)
Article
Multidisciplinary Sciences
Wison Laochareonsuk, Kanita Kayasut, Komwit Surachat, Piyawan Chiengkriwate, Surasak Sangkhathat
Summary: Genetic association and biological interaction analysis revealed the involvement of EFEMP1 SNPs in biliary atresia (BA) and their additive effect on BA risk when combined with ADD3 variants. Additionally, rs6761893 in EFEMP1 was indicative of survival in Thai BA patients.
SCIENTIFIC REPORTS
(2022)
Article
Pharmacology & Pharmacy
Xiaodong Zeng, Yuqin Liao, Xue Qiao, Ke Liang, Qiusi Luo, Mingbo Deng, Yishen Liu, Weijing Zhang, Xuechuan Hong, Yuling Xiao
Summary: Biliary atresia is a rare infant disease with challenging early diagnosis. A novel NIR-II fluorescence probe has been developed for efficient early diagnosis using simple fecal samples.
ACTA PHARMACEUTICA SINICA B
(2023)
Article
Multidisciplinary Sciences
Xi Li, Yan Li, Jintao Xiao, Huiwen Wang, Yan Guo, Xiuru Mao, Pan Shi, Yanliang Hou, Xiaoxun Zhang, Nan Zhao, Minghua Zheng, Yonghong He, Jingjing Ding, Ya Tan, Min Liao, Ling Li, Ying Peng, Xuan Li, Qiong Pan, Qiaoling Xie, Qiao Li, Jianwei Li, Ying Li, Zhe Chen, Yongxiu Huang, David N. Assis, Shi-Ying Cai, James L. Boyer, Xuequan Huang, Can-E Tang, Xiaowei Liu, Shifang Peng, Jin Chai
Summary: The numbers of DUOX2(+)ACE2(+) small cholangiocytes are inversely associated with disease severity in PBC. They may be the target of pIgR-mediated humoral responses. Protecting these cells and targeting anti-pIgR autoantibodies could be valuable strategies for therapeutic interventions in PBC.
NATURE COMMUNICATIONS
(2023)
Article
Oncology
Francois Bertucci, Vincent Niziers, Alexandre de Nonneville, Pascal Finetti, Lena Mescam, Olivier Mir, Antoine Italiano, Axel Le Cesne, Jean-Yves Blay, Michele Ceccarelli, Davide Bedognetti, Daniel Birnbaum, Emilie Mamessier
Summary: This study investigated the impact of immunologic constant of rejection (ICR) on the prognostic assessment of early-stage soft-tissue sarcomas (STS). The results showed that ICR signature was associated with patient age, pathological type, and tumor depth, and remained independently associated with metastasis-free survival (MFS) in multivariate analysis. A prognostic clinicogenomic model was also built, integrating ICR, Complexity Index in Sarcomas (CINSARC), and pathological type, and different systemic therapies were suggested for each prognostic group.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Gastroenterology & Hepatology
Surya P. Amarachintha, Reena Mourya, Hiroaki Ayabe, Li Yang, Zhenhua Luo, Xiaofeng Li, Unmesha Thanekar, Pranavkumar Shivakumar, Jorge A. Bezerra
Summary: The study investigated the mechanisms linked to abnormal cholangiocyte development in biliary atresia by generating biliary organoids from liver biopsies. The organoids showed evidence of halted epithelial development and structural defects in cholangiocyte-like cells from biliary atresia. Treatment with EGF and FGF2 resulted in the restoration of differentiation and functional markers, improved cell-cell junction, and decreased epithelial permeability in biliary atresia organoids.
Article
Respiratory System
Amit Kumar, Evan Elko, Sierra R. Bruno, Zoe F. Mark, Nicolas Chamberlain, Bethany Korwin Mihavics, Ravishankar Chandrasekaran, Joseph Walzer, Mona Ruban, Clarissa Gold, Ying Wai Lam, Sudhir Ghandikota, Anil G. Jegga, Jose L. Gomez, Yvonne M. W. Janssen-Heininger, Vikas Anathy
Summary: The study found that PDIA3 and SCGB1A1 are upregulated in IPF patients and correlate with a decrease in lung function. In a mouse model of lung fibrosis, it was shown that PDIA3 increases in SCGB1A1 cells. Specific deletion of PDIA3 in club cells resulted in a decrease in SCGB1A1 cells and fibrosis in mice.
Article
Pediatrics
Lauren Bradford, Mindy K. Ross, Jagila Minso, Mateja Cernelc-Kohan, Katayoon Shayan, Simon S. Wong, Xiaoping Li, Lauraine Rivier, Anil G. Jegga, Gail H. Deutsch, Timothy J. Vece, Ceila E. Loughlin, William A. Gower, Caitlin Hurley, Wayne Furman, Dennis Stokes, James S. Hagood
Summary: Three patients with Rubinstein-Taybi syndrome (RSTS) developed childhood interstitial lung disease (ILD), showing lung histopathology results consistent with ILD. Immunofluorescent staining suggested two potential mechanisms for ILD development: abnormal surfactant metabolism and/or persistent activation of myofibroblasts, both of which could be related to dysfunctional CREBBP protein.
PEDIATRIC PULMONOLOGY
(2022)
Article
Cardiac & Cardiovascular Systems
Yuliang Feng, Liuyang Cai, Wanzi Hong, Chunxiang Zhang, Ning Tan, Mingyang Wang, Cheng Wang, Feng Liu, Xiaohong Wang, Jianyong Ma, Chen Gao, Mohit Kumar, Yuanxi Mo, Qingshan Geng, Changjun Luo, Yan Lin, Haiyang Chen, Shuang-Yin Wang, Michael J. Watson, Anil G. Jegga, Roger A. Pedersen, Ji-Dong Fu, Zhao Wang, Guo-Chang Fan, Sakthivel Sadayappan, Yigang Wang, Siim Pauklin, Feng Huang, Wei Huang, Lei Jiang
Summary: This study investigates the role of 3-dimensional chromatin topology in dilated cardiomyopathy (DCM) by analyzing the epigenome and transcriptome maps of DCM and nonfailing heart tissues. The research reveals that the reprogramming of chromatin topology is associated with transcriptional dysregulation in DCM, with the key transcription factor HAND1 implicated in the process. The findings provide insights into the pathogenesis of DCM and highlight the importance of chromatin organization in heart failure.
Article
Gastroenterology & Hepatology
Ingrid Jurickova, Erin Bonkowski, Elizabeth Angerman, Elizabeth Novak, Alex Huron, Grayce Akers, Kentaro Iwasawa, Tzipi Braun, Rotem Hadar, Maria Hooker, Sarah Han, David J. Cutler, David T. Okou, Subra Kugathasan, Anil Jegga, James Wells, Takanori Takebe, Kevin P. Mollen, Yael Haberman, Lee A. Denson
Summary: This study investigated the regulation of pathways implicated in stricture formation using a patient-specific human intestinal organoid model system. The results showed that the microbial metabolite butyrate and eicosatetraynoic acid have a significant effect on mitochondrial function, wound healing, and tissue stiffness, suggesting their potential as therapeutic targets for pediatric Crohn's disease patients.
INFLAMMATORY BOWEL DISEASES
(2022)
Article
Biochemistry & Molecular Biology
Sudhir Ghandikota, Mihika Sharma, Harshavardhana H. Ediga, Satish K. Madala, Anil G. Jegga
Summary: This study analyzed lung transcriptomic data to identify gene modules associated with idiopathic pulmonary fibrosis (IPF) and identified potential biomarkers. Validation studies confirmed the correlation of CRABP2 expression with decline in lung function.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Gastroenterology & Hepatology
Kathryn Clarkston, Rebekah Karns, Anil G. Jegga, Mihika Sharma, Sejal Fox, Babajide A. Ojo, Phillip Minar, Thomas D. Walters, Anne M. Griffiths, David R. Mack, Brendan Boyle, Neal S. LeLeiko, James Markowitz, Joel R. Rosh, Ashish S. Patel, Sapana Shah, Robert N. Baldassano, Marian Pfefferkorn, Cary Sauer, Subra Kugathasan, Yael Haberman, Jeffrey S. Hyams, Lee A. Denson, Michael J. Rosen
Summary: This study aimed to predict clinical outcomes in pediatric ulcerative colitis (UC) through assessing gene expression and investigate the potential pathogenic roles of predictive genes. IL13RA2 was associated with corticosteroid-free remission, while RORC was associated with a lower likelihood of colectomy. RNA sequencing and immunostaining supported these findings.
JOURNAL OF CROHNS & COLITIS
(2022)
Article
Genetics & Heredity
Darshini A. Desai, Vinay J. Rao, Anil G. Jegga, Perundurai S. Dhandapany, Sakthivel Sadayappan
Summary: This study systematically assessed the evolutionary and epigenetic patterns of MYBPC family mutations using a machine learning approach. The results revealed the impact and pathogenicity of these mutations on MyBP-C protein structure, as well as their evolutionary and epigenetic patterns. Specific findings include arginine as the most mutated amino acid, C5 and C6 domains as hotspots for mutations, and a high percentage of truncations in cMyBP-C.
FRONTIERS IN GENETICS
(2022)
Article
Biochemical Research Methods
Jaswanth K. Yella, Anil G. Jegga
Summary: This article introduces a strategy of drug repositioning and predicting new indications using computational methods, and proposes a new approach based on the multi-view graph attention network. This method outperforms four other state-of-the-art methods and demonstrates its potential value in drug discovery through experimental verification.
IEEE-ACM TRANSACTIONS ON COMPUTATIONAL BIOLOGY AND BIOINFORMATICS
(2022)
Article
Gastroenterology & Hepatology
Abigail E. Russi, Pranavkumar Shivakumar, Zhenhua Luo, Jorge A. Bezerra
Summary: This study investigates the mechanisms by which different subpopulations of type 2 innate lymphoid cells (ILC2s) regulate the response of biliary epithelial cells to injury. The results demonstrate that natural ILC2s are positively associated with cholangiocyte abundance and that they promote epithelial proliferation through the IL-13/IL-4Rα/STAT6 pathway. This pathway plays a crucial role in maintaining epithelial homeostasis and promoting repair in experimental biliary atresia.
Article
Biochemistry & Molecular Biology
Vi Nguyen, Jacob Kravitz, Chao Gao, Marcelo L. Hochman, Dehao Meng, Dongbao Chen, Yunguan Wang, Anil G. Jegga, J. Stuart Nelson, Wenbin Tan
Summary: In this study, metabolites associated with Port Wine Birthmark (PWB)-derived induced pluripotent stem cells (iPSCs) were explored. The analysis identified differential metabolites, such as upregulated glutathione and downregulated sphingolipid metabolism, in PWB iPSCs compared to normal ones. Key molecules associated with glutathione metabolism were also found to be upregulated in PWB vasculatures. Additionally, other affected metabolic pathways in PWB iPSCs were identified. These findings contribute to a better understanding of the pathogenesis of PWB and the development of potential treatment strategies.
Article
Oncology
Kyu Shik Mun, Jaimie D. Nathan, Anil G. Jegga, Kathryn A. Wikenheiser-Brokamp, Maisam Abu-El-Haija, Anjaparavanda P. Naren
Summary: We report a rare case of a cystic fibrosis patient with debilitating abdominal pain. By testing drugs on patient-derived organoids, we discovered that ivacaftor can improve the impaired pancreatic function caused by this mutation.
AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH
(2022)
Meeting Abstract
Oncology
Cheng-Yu Tsai, Toshie Saito, Mayur Sarangdhar, Maisam Abu-El-Haija, Li Wen, Bomi Lee, Murli Manohar, Monique T. Barakat, Kevin Contrepois, Na Bo, Ying Ding, Kristen E. Stevenson, Elena Ladas, Lewis B. Silverman, Loredana Quadro, Tracy G. Anthony, Anil Goud Jegga, Sohail Z. Husain
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Article
Gastroenterology & Hepatology
Kyu Shik Mun, Jaimie D. Nathan, Tom K. Lin, Deborah A. Elder, Anil G. Jegga, Anjaparavanda P. Naren, Maisam Abu-El-Haija
Summary: Total pancreatectomy with islet autotransplantation (TPIAT) is a surgical option for chronic pancreatitis, and for patients with type 1 diabetes, transplantation of islets can alleviate abdominal pain, reduce opioid use, and potentially lower the dosage of insulin.
Meeting Abstract
Gastroenterology & Hepatology
Y. Haberman Ziv, T. Braun, K. Sosnovski, A. Amir, K. VanDussen, I. U. Igor Ulitsky, A. Griffiths, T. Walters, D. Mack, B. Boyle, S. Kugathasan, A. Jegga, J. Hyams, L. Denson
JOURNAL OF CROHNS & COLITIS
(2022)