Article
Cell Biology
Badal C. Roy, Ishfaq Ahmed, Jason Stubbs, Jun Zhang, Thomas Attard, Seth Septer, Danny Welch, Shrikant Anant, Venkatesh Sampath, Shahid Umar
Summary: The alternative promoter usage generates long and short isoforms of DCLK1, which plays a critical role in regulating mucosal immune responses to infection. The Notch1-DCLK1 axis may be integral to the development of murine or human colitis.
CELL DEATH DISCOVERY
(2021)
Article
Multidisciplinary Sciences
Carolyn Bomidi, Matthew Robertson, Cristian Coarfa, Mary K. Estes, Sarah E. Blutt
Summary: Intestinal epithelial damage is associated with most digestive diseases, impacting nutrient absorption, hormone production, and antimicrobial defense. Understanding epithelial repair and regeneration is crucial for developing therapeutics. Research shows that stem cells drive a repair program, involving tuft cells and immature enterocytes in the repair of damaged epithelium.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Medicine, Research & Experimental
Kathrin Liszt, Qiaoling Wang, Mona Farhadipour, Anneleen Segers, Theo Thijs, Linda Nys, Ellen Deleus, Bart van der Schueren, Christopher Gerner, Benjamin Neuditschko, Laurens J. Ceulemans, Matthias Lannoo, Jan Tack, Inge Depoortere
Summary: Taste 2 receptors (TAS2Rs) in the human gut play a key role in detecting potentially toxic food. The study found that human jejunal crypts, especially in individuals with obesity, respond to bitter substances by releasing antimicrobial peptides and regulating other immune factors that affect the growth of E. coli. The study also identified the role of TAS2R43 in the effects of aloin on E. coli growth and mucus glycoprotein release. Additionally, the study revealed the potential of TAS2Rs as a target for treating diseases related to the immune system and body weight control.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Biochemistry & Molecular Biology
Maria-Theodora Melissari, Ana Henriques, Christos Tzaferis, Alejandro Prados, Michalis E. Sarris, Niki Chalkidi, Dimitra Mavroeidi, Panagiotis Chouvardas, Sofia Grammenoudi, George Kollias, Vasiliki Koliaraki
Summary: This study investigates the various subsets of intestinal mesenchymal cells and their roles in intestinal morphogenesis and pathophysiology. The results show that Col6a1(Cre) mouse targets fibroblast subsets and perivascular cells, as well as mesenchymal aggregates crucial for intestinal development. In adulthood, Col6a1(+)/CD201(+) mesenchymal cells regulate enteroendocrine cell differentiation and epithelial proliferation. During acute colitis, they exhibit an inflammatory and extracellular matrix remodelling gene signature. However, these cells are dispensable for normal organ architecture in both homeostasis and tissue regeneration.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Multidisciplinary Sciences
Michael A. Schumacher, Jonathan J. Hsieh, Cambrian Y. Liu, Keren L. Appel, Amanda Waddell, Dana Almohazey, Kay Katada, Jessica K. Bernard, Edie B. Bucar, Safina Gadeock, Kathryn M. Maselli, M. Kay Washington, Tracy C. Grikscheit, David Warburton, Michael J. Rosen, Mark R. Frey
Summary: The loss of the intracellular signaling regulator Sprouty2 in intestinal epithelial cells is a protective response to injury that leads to increased secretory cell numbers, thus limiting the severity of colitis.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Sonia Jimeno, Rosario Prados-Carvajal, Maria Jesus Fernandez-Avila, Sonia Silva, Domenico Alessandro Silvestris, Martin Endara-Coll, Judit Domingo-Prim, Fernando Mejias-Navarro, Guillermo Rodriguez-Real, Amador Romero-Franco, Silvia Jimeno-Gonzalez, Sonia Barroso, Valeriana Cesarini, Andres Aguilera, Angela Gallo, Neus Visa, Pablo Huertas
Summary: Specific RNA-related factors, including the RNA-editing enzyme ADAR2, play important roles in DNA repair. The researchers found that RNA editing is involved in the response to DNA damage, with a phenomenon called the RNA Editing DAmage Response (REDAR) being observed. REDAR relies on the checkpoint kinase ATR and the recombination factor CtIP, and depletion of ADAR2 leads to increased cellular sensitivity to genotoxic agents and impaired homologous recombination.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Stavroula Tsaridou, Georgia Velimezi, Frances Willenbrock, Maria Chatzifrangkeskou, Waheba Elsayed, Andreas Panagopoulos, Dimitris Karamitros, Vassilis Gorgoulis, Zoi Lygerou, Vassilis Roukos, Eric O'Neill, Dafni Eleftheria Pefani
Summary: This study identified a novel role for the tumor suppressor RASSF1A at rDNA break sites, providing mechanistic insight into how the DNA damage response is organized in a chromatin context and further evidence for how silencing of the RASSF1A tumor suppressor contributes to genome instability.
Article
Pathology
Wencke Reineking, Ida E. Schauerte, Johannes Junginger, Marion Hewicker-Trautwein
Summary: This study investigated the immunoreactivity of potential intestinal stem cell markers and tuft cell marker in normal canine intestine and intestinal epithelial neoplasms. It was found that the immunoreactivity of stem cell markers was increased in canine intestinal adenomas and adenocarcinomas compared with normal mucosa.
VETERINARY PATHOLOGY
(2022)
Article
Cell Biology
Justine Creff, Ada Nowosad, Anne Prel, Anne Pizzoccaro, Marion Aguirrebengoa, Nicolas Duquesnes, Caroline Callot, Thomas Jungas, Christine Dozier, Arnaud Besson
Summary: p57Kip2 is a cyclin/CDK inhibitor that regulates intestinal stem cell (ISC) fate and proliferation in a CDK-independent manner. In the absence of p57, there is increased proliferation of intestinal crypts and amplification of transit-amplifying cells and Hopx+ ISCs. RNA sequencing analyses reveal significant gene expression changes in Hopx+ ISCs upon p57 depletion. Furthermore, p57 binds to and inhibits the activity of Ascl2, a transcription factor critical for ISC specification and maintenance, by recruiting a corepressor complex. Hence, p57 plays a key role in maintaining Hopx+ ISC quiescence and repressing the ISC phenotype by inhibiting Ascl2 in a CDK-independent manner during intestinal development.
Article
Genetics & Heredity
Tsutomu Shimura
Summary: AT is a disease characterized by extreme sensitivity to ionizing radiation, with AT patients and ATM-deficient mice displaying intrinsic mitochondrial dysfunction. ATM plays a critical role in maintaining cellular redox homeostasis.
Article
Cell & Tissue Engineering
Junquan Tian, Yuying Li, Xuetai Bao, Fan Yang, Xiongzhuo Tang, Qian Jiang, Chengbo Yang, Yulong Yin, Kang Yao
Summary: Early weaning disrupts intestinal epithelial development and increases the risk of gastrointestinal diseases. Glutamine (Gln), found in plasma and milk, has been reported to have positive effects on intestinal health. This study investigated the impact of Gln on intestinal stem cell (ISC) activity in response to early weaning. The results show that Gln improves early weaning-induced epithelial atrophy and enhances ISC-mediated epithelial regeneration by augmenting WNT signaling.
Article
Nutrition & Dietetics
Wusun Li, Yingying Lin, Yujia Luo, Yuqi Wang, Yao Lu, Yixuan Li, Huiyuan Guo
Summary: Vitamin D mediated through VDR protects against IR-induced intestinal injury by inhibiting apoptosis of crypt stem/progenitor cells. VDR deficiency may lead to more severe DNA damage and apoptosis, impairing intestinal regeneration and survival time. Targeting VDR could be an effective strategy for treatment of gastrointestinal syndrome in clinical radiation therapy.
Article
Food Science & Technology
Anrong Wang, Xinyi Liang, Wanxia Chen, Yiting Liu, Yiping Zhu, Dong Zhang, Ling Hu, Ruliu Li
Summary: The study investigated the potential effects of total ginsenosides (TG) in intestinal mucosal restitution. TG reversed cell growth inhibition caused by DFMO and promoted cell proliferation by affecting the translation of c-Myc. Furthermore, Panax ginseng aqueous extract (PGE) prevented intestinal mucosal injury and promoted mucosal restitution through enhancing HuR and c-Myc levels.
Article
Immunology
Wanlin Cui, Yuji Nagano, Satoru Morita, Takeshi Tanoue, Hidehiro Yamane, Keiko Ishikawa, Toshiro Sato, Masato Kubo, Shohei Hori, Tadatsugu Taniguchi, Masanori Hatakeyama, Koji Atarashi, Kenya Honda
Summary: A novel ILC2 subset that constitutively expresses IL-4 was identified in the mouse intestine. The absence of gut microbiota had marginal effects, but feeding mice with a vitamin B1-deficient diet compromised the number of intestinal IL-4(+) ILC2s.
JOURNAL OF EXPERIMENTAL MEDICINE
(2023)
Article
Oncology
Conor Hanna, Victoria L. Dunne, Steven M. Walker, Karl T. Butterworth, Nuala McCabe, David J. J. Waugh, Richard D. Kennedy, Kevin M. Prise
Summary: Prostate cancer is the most frequently diagnosed cancer in men, with the role of the PTEN gene being complex but important in its treatment. Studies suggest that in the absence of PTEN, combined treatment using radiotherapy and the ATM inhibitor KU-60019 has a greater therapeutic effect.
Article
Oncology
Xiangyan Wu, Dongfeng Qu, Nathaniel Weygant, Jun Peng, Courtney W. Houchen
Article
Oncology
Anita L. Ray, Robert A. Nofchissey, Maaz A. Khan, Megan A. Reidy, Megan R. Lerner, Xiangyan Wu, Shaoxuan Guo, Spencer L. Hill, Nathaniel Weygant, Sarah F. Adams, Eliseo F. Castillo, William L. Berry, Michael B. Stout, Katherine T. Morris
BRITISH JOURNAL OF CANCER
(2020)
Article
Oncology
Parthasarathy Chandrakesan, Janani Panneerselvam, Randal May, Nathaniel Weygant, Dongfeng Qu, William R. Berry, Kamille Pitts, Ben Z. Stanger, Chinthalapally Rao, Michael S. Bronze, Courtney W. Houchen
MOLECULAR CANCER THERAPEUTICS
(2020)
Article
Oncology
Janani Panneerselvam, Priyanga Mohandoss, Ravi Patel, Hamza Gillan, Michael Li, Kirtana Kumar, DangHuy Nguyen, Nathaniel Weygant, Dongfeng Qu, Kamille Pitts, Stanley Lightfoot, Chinthalapally Rao, Courtney Houchen, Michael Bronze, Parthasarathy Chandrakesan
MOLECULAR THERAPY-ONCOLYTICS
(2020)
Article
Cell Biology
Zeyu Wang, Guanhua Su, Ziyu Dai, Ming Meng, Hao Zhang, Fan Fan, Zhengzheng Liu, Longbo Zhang, Nathaniel Weygant, Fengqiong He, Ning Fang, Liyang Zhang, Quan Cheng
Summary: Circadian clock gene expression in glioma is associated with disease progression, affecting the tumor immune landscape and cell cycle, potentially impacting survival outcomes. A risk model can predict glioma survival outcomes and may be applicable to other types of cancer.
CELL PROLIFERATION
(2021)
Article
Gastroenterology & Hepatology
Nathaniel Weygant, Karen Chang, Christian S. Jackson, Kenneth J. Vega
Summary: This study used the TCGA EC dataset to analyze whether survival rates vary by sex in esophageal cancer patients, finding that male patients have lower survival rates, and some genetic alterations are dysregulated in patients of different sexes.
CLINICAL AND TRANSLATIONAL GASTROENTEROLOGY
(2021)
Article
Oncology
Liyang Zhang, Fangkun Liu, Nathaniel Weygant, Junxia Zhang, Ping Hu, Zailong Qin, Jingxuan Yang, Quan Cheng, Fan Fan, Yu Zeng, Yongjian Tang, Yusheng Li, Anliu Tang, Fengqiong He, Jun Peng, Weihua Liao, Zhongliang Hu, Min Li, Zhixiong Liu
Summary: Researchers developed an integrated system using patient-derived glioma cerebral organoids and xenograft models to understand glioma biology and predict response to chemotherapy drugs, providing a new strategy for personalized treatment of this deadly disease.
Review
Cell Biology
Xingmin Wang, Ram Babu Undi, Naushad Ali, Mark M. Huycke
Summary: Sporadic colorectal cancer (CRC) is a major cause of global cancer mortality, with the gut microbiota recently recognized as a significant contributing factor. The microbiota-induced bystander effect (MIBE) is a newly described cancer mechanism where microbiota-driven parainflammation leads to the cancerous transformation of colon epithelial cells. Understanding the interactions between gut microbiota and mucosal immune effector cells that generate bystander effects may offer insights into CRC prevention.
DISEASE MODELS & MECHANISMS
(2021)
Review
Oncology
Ling Ding, Yuning Yang, Qin Lu, Zhiyun Cao, Nathaniel Weygant
Summary: This review summarizes the application of human colorectal cancer patient-derived organoids (PDOs) in the study of cancer stem cells (CSCs) and the cancer stem cell niche. It focuses on the relevance of PDOs in understanding CSC-related signaling, interactions between CSCs and the tumor microenvironment, and the modeling of CSC-driven resistance to therapies.
CURRENT CANCER DRUG TARGETS
(2022)
Article
Oncology
Yang Ge, Xiaona Fan, Xuying Huang, Nathaniel Weygant, Zeru Xiao, Rui Yan, Heshu Liu, Jian Liu, Guangyu An, Jiannan Yao
Summary: DCLK1-S expression is significantly increased in human esophageal squamous cell carcinoma (ESCC) tissues and is associated with malignant progression and poor prognosis. Functional studies showed that DCLK1-S plays a role in promoting ESCC cell proliferation, migration, and invasion, potentially through the MAPK/ERK/MMP2 pathway. These findings suggest that DCLK1-S may serve as a biomarker or therapeutic target for improving outcomes in patients with ESCC.
MOLECULAR CANCER RESEARCH
(2021)
Article
Oncology
Ling Ding, Yuning Yang, Yang Ge, Qin Lu, Zixing Yan, Xuzheng Chen, Jian Du, Sassan Hafizi, Xiaohui Xu, Jiannan Yao, Jian Liu, Zhiyun Cao, Nathaniel Weygant
Summary: This study demonstrates that the small molecule kinase inhibitor DCLK1-IN-1 effectively inhibits DCLK1 phosphorylation and stemness related properties of RCC cells, showing potential as an immunotherapy agent and in combination therapy with anti-PD1. Clinical analysis suggests that DCLK1 predicts RCC survival and its expression is correlated with immune cell infiltration and immunosuppressive macrophage populations.
Article
Virology
Ram Babu Undi, Jason L. Larabee, Adrian Filiberti, Susanna Ulahannan, Sheeja Aravindan, Edana Stroberg, Lisa M. Barton, Eric J. Duval, Sanjay Mukhopadhyay, James C. Henthorn, Darrin Akins, Courtney W. Houchen, Mark M. Huycke, Naushad Ali
Summary: COVID-19 mortality is higher in patients with underlying comorbidities such as chronic liver diseases. This study shows that DCLK1 plays a crucial role in enhancing SARS-CoV-2 viremia, inflammatory cytokine expression, and dysregulation of immune cells involved in innate immunity. DCLK1 may be a potential therapeutic target for COVID-19, especially in patients with comorbidities associated with DCLK1 expression.
JOURNAL OF VIROLOGY
(2022)
Review
Oncology
Ram Babu Undi, Adrian Filiberti, Naushad Ali, Mark M. Huycke
Summary: Inflammation is a key characteristic of cancer, and macrophages play a crucial role in chronic inflammation, parainflammation, and inflammaging. Regardless of whether it is induced by infection, injury, or aging, immune dysregulation and chronic macrophage polarization contribute to cancer initiation by producing proinflammatory chemokines/cytokines and genotoxins, and by modulating immune surveillance. This review presents both pre-clinical and clinical evidence supporting polarized macrophages as endogenous cellular carcinogens in the context of chronic inflammation, parainflammation, and inflammaging. Additionally, emerging strategies for cancer prevention targeting macrophage function and phenotype, such as small molecule inhibitors and probiotic approaches, are discussed.
Article
Biochemistry & Molecular Biology
Ling Ding, Yuning Yang, Qin Lu, Dongfeng Qu, Parthasarathy Chandrakesan, Hailan Feng, Hong Chen, Xuzheng Chen, Zhuhui Liao, Jian Du, Zhiyun Cao, Nathaniel Weygant
Summary: This study investigates the function and mechanism of bufalin against colorectal cancer stemness. The results demonstrate that bufalin inhibits CRC stemness by targeting the C-Kit/Slug signaling axis, leading to inhibited CRC growth and progression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Medicine, General & Internal
Ling Zhang, Qiaoyan Cai, Shan Lin, Bin Chen, Beibei Jia, Renzhi Ye, Nathaniel Weygant, Jianfeng Chu, Jun Peng
Summary: The study demonstrates that Qingda granule has a significant neuroprotective effect on ischemic stroke, improving neurobehavioral deficits, reducing neuron loss, and inhibiting apoptosis. Furthermore, Qingda granule acts through modulating the lncRNA GAS5/miR-137 signaling pathway.
INTERNATIONAL JOURNAL OF MEDICAL SCIENCES
(2021)