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JOURNAL ARTICLE
Simon Guignard, Mahmoud Saifeddine, Koichiro Mihara, Majid Motahhary, Magali Savignac, Laura Guiraud, David Sagnat, Mireille Sebbag, Sokchea Khou, Corinne Rolland, Anissa Edir, Barbara Bournet, Louis Buscail, Etienne Buscail, Laurent Alric, Caroline Camare, Mouna Ambli, Nathalie Vergnolle, Morley D Hollenberg, Céline Deraison, Chrystelle Bonnart
BACKGROUND AND PURPOSE: Chymotrypsin is a pancreatic protease secreted into the lumen of the small intestine to digest food proteins. We hypothesized that chymotrypsin activity may be found close to epithelial cells and that chymotrypsin signals to them via protease-activated receptors (PARs). We deciphered molecular pharmacological mechanisms and gene expression regulation for chymotrypsin signalling in intestinal epithelial cells. EXPERIMENTAL APPROACH: The presence and activity of chymotrypsin were evaluated by Western blot and enzymatic activity tests in the luminal and mucosal compartments of murine and human gut samples...
April 18, 2024: British Journal of Pharmacology
#2
JOURNAL ARTICLE
Jinxia Liu, Jane MacNaughtan, Annarein J C Kerbert, Theo Portlock, Javier Martínez Gonzalez, Yi Jin, Frederick Clasen, Abeba Habtesion, Huoyan Ji, Qin Jin, Alexandra Phillips, Francesco De Chiara, Ganesh Ingavle, Cesar Jimenez, Giacomo Zaccherini, Katherine Husi, Miguel Angel Rodriguez Gandia, Paul Cordero, Junpei Soeda, Lynda McConaghy, Jude Oben, Karen Church, Jia V Li, Haifeng Wu, Aarti Jalan, Pere Gines, Elsa Solà, Simon Eaton, Carrie Morgan, Michal Kowalski, Daniel Green, Amir Gander, Lindsey A Edwards, I Jane Cox, Helena Cortez-Pinto, Thomas Avery, Reiner Wiest, Francois Durand, Paolo Caraceni, Roberto Elosua, Joan Vila, Marco Pavesi, Vicente Arroyo, Nathan Davies, Rajeshwar P Mookerjee, Victor Vargas, Susan Sandeman, Gautam Mehta, Saeed Shoaie, Julian Marchesi, Agustín Albillos, Fausto Andreola, Rajiv Jalan
OBJECTIVE: Targeting bacterial translocation in cirrhosis is limited to antibiotics with risk of antimicrobial resistance. This study explored the therapeutic potential of a non-absorbable, gut-restricted, engineered carbon bead adsorbent, Yaq-001 in models of cirrhosis and acute-on-chronic liver failure (ACLF) and, its safety and tolerability in a clinical trial in cirrhosis. DESIGN: Performance of Yaq-001 was evaluated in vitro . Two-rat models of cirrhosis and ACLF, (4 weeks, bile duct ligation with or without lipopolysaccharide), receiving Yaq-001 for 2 weeks; and two-mouse models of cirrhosis (6-week and 12-week carbon tetrachloride (CCl4)) receiving Yaq-001 for 6 weeks were studied...
April 15, 2024: Gut
#3
JOURNAL ARTICLE
Feifei Zhang, Varun Sahu, Ke Peng, Yichen Wang, Tianxia Li, Pratyusha Bala, Daulet Aitymbayev, Pranshu Sahgal, Antje Schaefer, Channing J Der, Sandra Ryeom, Sam Yoon, Nilay Sethi, Adam J Bass, Haisheng Zhang
OBJECTIVE: Genomic studies of gastric cancer have identified highly recurrent genomic alterations impacting RHO signalling, especially in the diffuse gastric cancer (DGC) histological subtype. Among these alterations are interchromosomal translations leading to the fusion of the adhesion protein CLDN18 and RHO regulator ARHGAP26. It remains unclear how these fusion constructs impact the activity of the RHO pathway and what is their broader impact on gastric cancer development. Herein, we developed a model to allow us to study the function of this fusion protein in the pathogenesis of DGC and to identify potential therapeutic targets for DGC tumours with these alterations...
April 15, 2024: Gut
#4
REVIEW
Siyao Wang, Xu Gong, Fei Xiao, Yun Yang
Microbial communities in the human gut play a significant role in regulating host gene expression, influencing a variety of biological processes. To understand the molecular mechanisms underlying host-microbe interactions, tools that can dissect signaling networks are required. In this review, we discuss recent advances in molecular tools used to study this interplay, with a focus on those that explore how the microbiome regulates host gene expression. These tools include CRISPR-based whole-body genetic tools for deciphering host-specific genes involved in the interaction process, Cre- loxP based tissue/cell-specific gene editing approaches, and in vitro models of host-derived organoids...
2024: Frontiers in Microbiology
#5
JOURNAL ARTICLE
Anthony Chin Yang Su, Xiao Ding, Harry Cheuk Hay Lau, Xing Kang, Qing Li, Xueliang Wang, Yali Liu, Lanping Jiang, Yinghong Lu, Weixin Liu, Yanqiang Ding, Alvin Ho-Kwan Cheung, Ka Fai To, Jun Yu
OBJECTIVE: Probiotic Lactococcus lactis is known to confer health benefits to humans. Here, we aimed to investigate the role of L. lactis in colorectal cancer (CRC). DESIGN: L. lactis abundance was evaluated in patients with CRC (n=489) and healthy individuals (n=536). L. lactis was isolated from healthy human stools with verification by whole genome sequencing. The effect of L. lactis on CRC tumourigenesis was assessed in transgenic Apc Min/+ mice and carcinogen-induced CRC mice...
April 10, 2024: Gut
#6
JOURNAL ARTICLE
Brooke Wang, Lilianne Iglesias-Ledon, Matthew Bishop, Anushka Chadha, Sara E Rudolph, Brooke N Longo, Dana M Cairns, Ying Chen, David L Kaplan
The development of patient-derived intestinal organoids represents an invaluable model for simulating the native human intestinal epithelium. These stem cell-rich cultures outperform commonly used cell lines like Caco-2 and HT29-MTX in reflecting the cellular diversity of the native intestinal epithelium after differentiation. In our recent study examining the effects of polystyrene (PS), microplastics (MPs), and nanoplastics (NPs), widespread pollutants in our environment and food chain, on the human intestinal epithelium, these organoids have been instrumental in elucidating the absorption mechanisms and potential biological impacts of plastic particles...
April 2024: Current protocols
#7
JOURNAL ARTICLE
Eun-Jung Kang, Jae-Hoon Kim, Young Eun Kim, Hana Lee, Kwang Bo Jung, Dong-Ho Chang, Youngjin Lee, Shinhye Park, Eun-Young Lee, Eun-Ji Lee, Ho Bum Kang, Moon-Young Rhyoo, Seungwoo Seo, Sohee Park, Yubin Huh, Jun Go, Jung Hyeon Choi, Young-Keun Choi, In-Bok Lee, Dong-Hee Choi, Yun Jeong Seo, Jung-Ran Noh, Kyoung-Shim Kim, Jung Hwan Hwang, Ji-Seon Jeong, Ha-Jeong Kwon, Hee Min Yoo, Mi-Young Son, Yeon-Gu Kim, Dae-Hee Lee, Tae-Young Kim, Hyo-Jung Kwon, Myung Hee Kim, Byoung-Chan Kim, Yong-Hoon Kim, Dukjin Kang, Chul-Ho Lee
Akkermansia muciniphila has received great attention because of its beneficial roles in gut health by regulating gut immunity, promoting intestinal epithelial development, and improving barrier integrity. However, A. muciniphila-derived functional molecules regulating gut health are not well understood. Microbiome-secreted proteins act as key arbitrators of host-microbiome crosstalk through interactions with host cells in the gut and are important for understanding host-microbiome relationships. Herein, we report the biological function of Amuc_1409, a previously uncharacterised A...
April 6, 2024: Nature Communications
#8
JOURNAL ARTICLE
Gawoon Shim, Isaac B Breinyn, Alejandro Martínez-Calvo, Sameeksha Rao, Daniel J Cohen
Epithelial tissues sheath organs and electro-mechanically regulate ion and water transport to regulate development, homeostasis, and hydrostatic organ pressure. Here, we demonstrate how external electrical stimulation allows us to control these processes in living tissues. Specifically, we electrically stimulate hollow, 3D kidneyoids and gut organoids and find that physiological-strength electrical stimulation of ∼ 5 - 10 V/cm powerfully inflates hollow tissues; a process we call electro-inflation...
April 5, 2024: Nature Communications
#9
JOURNAL ARTICLE
Yu Jia, Ge Zhu, Cheng Qiu, Jun-Mei Lai, Ye Shen, Shu-Wen Jin, Xue Yang, Hai-Ping Zhu, Bang-Chuan Hu, Xiang-Ming Ye, Shi-Jing Mo
AIMS: Intestinal barrier dysfunction is the initial and propagable factor of sepsis in which acute kidney injury (AKI) has been considered as a common life-threatening complication. Our recent study identifies the regulatory role of Pellino1 in tubular death under inflammatory conditions in vitro. The objective of our current study is to explore the impact of Pellino1 on gut-kidney axis during septic AKI and uncover the molecular mechanism (s) underlying this process. MATERIALS AND METHODS: Immunohistochemistry (IHC) was conducted to evaluate Pellino1 and NOD-like receptor thermal protein domain associated protein 3 (NLRP3) levels in renal biopsies from critically ill patients with a clinical diagnosis of sepsis...
April 3, 2024: Life Sciences
#10
REVIEW
Tania Malonga, Nathalie Vialaneix, Martin Beaumont
The recent development of single cell transcriptomics highlighted the existence of a new lineage of mature absorptive cells in the human intestinal epithelium. This subpopulation is characterized by the specific expression of Bestrophin 4 (BEST4) and of other marker genes including OTOP2, CA7, GUCA2A, GUCA2B, and SPIB. BEST4+ cells appear early in development and are present in all regions of the small and large intestine at a low abundance (<5% of all epithelial cells). Location-specific gene expression profiles in BEST4+ cells suggest their functional specialization in each gut region, as exemplified by the small intestine-specific expression of the ion channel CFTR...
April 1, 2024: American Journal of Physiology. Cell Physiology
#11
JOURNAL ARTICLE
Organoids as a tool to study homeostatic and pathological immune-epithelial interactions in the gut.
Emma Højmose Kromann, Ainize Peña Cearra, Joana F Neves
The intestine hosts the largest immune cell compartment in the body as a result of its continuous exposure to exogenous antigens. The intestinal barrier is formed by a single layer of epithelial cells which separate immune cells from the gut lumen. Bidirectional interactions between the epithelium and the immune compartment are critical for maintaining intestinal homeostasis by limiting infection, preventing excessive immune activation, and promoting tissue repair processes. However, our understanding of epithelial-immune interactions incomplete as the complexity of in vivo models can hinder mechanistic studies, cell culture models lack the cellular heterogeneity of the intestine and when established from primary cell can be difficult to maintain...
March 29, 2024: Clinical and Experimental Immunology
#12
JOURNAL ARTICLE
Caihan Duan, Zhe Wang, Junhao Wu, Chen Tan, Feifei Fang, Wei Qian, Chaoqun Han, Xiaohua Hou
Fut2-mediated α1,2-fucosylation is important for gut homeostasis, including the intestinal stem cell (ISC). The stemness of ISC declines with age, and aging-associated ISC dysfunction is closely related to many age-related intestinal diseases. We previously found intestinal epithelial dysfunction in some aged Fut2 knockout mice. However, how Fut2-mediated α1,2-fucosylation affects ISC aging is still unknown. On this basis, the herein study aims to investigate the role of Fut2-mediated α1,2-fucosylation in ISC aging...
2024: Research: a science partner journal
#13
JOURNAL ARTICLE
Rosângela Salerno-Goncalves, Haiyan Chen, Andrea C Bafford, Mariana Izquierdo, Juan Carlos Hormazábal, Rosanna Lagos, Hervé Tettelin, Adonis D'Mello, Jayaum S Booth, Alessio Fasano, Myron M Levine, Marcelo B Sztein
Salmonella enterica serovar Typhi ( S . Typhi), a human-restricted pathogen, invades the host through the gut to cause typhoid fever. Recent calculations of the typhoid fever burden estimated that more than 10 million new typhoid fever cases occur in low and middle-income countries, resulting in 65,400-187,700 deaths yearly. Interestingly, if not antibiotic-treated, upon the resolution of acute disease, 1%-5% of patients become asymptomatic chronic carriers. Chronically infected hosts are not only critical reservoirs of infection that transmit the disease to naive individuals but are also predisposed to developing gallbladder carcinoma...
2024: Frontiers in Immunology
#14
JOURNAL ARTICLE
Ruta Inciuraite, Rolandas Gedgaudas, Rokas Lukosevicius, Deimante Tilinde, Rima Ramonaite, Alexander Link, Neringa Kasetiene, Mindaugas Malakauskas, Gediminas Kiudelis, Laimas Virginijus Jonaitis, Juozas Kupcinskas, Simonas Juzenas, Jurgita Skieceviciene
BACKGROUND: Despite extensive research on microbiome alterations in ulcerative colitis (UC), the role of the constituent stable microbiota remains unclear. RESULTS: This study, employing 16S rRNA-gene sequencing, uncovers a persistent microbial imbalance in both active and quiescent UC patients compared to healthy controls. Using co-occurrence and differential abundance analysis, the study highlights microbial constituents, featuring Phocaeicola, Collinsella, Roseburia, Holdemanella, and Bacteroides, that are not affected during the course of UC...
March 23, 2024: Gut Pathogens
#15
JOURNAL ARTICLE
Thomas U Greiner, Ara Koh, Eduard Peris, Mattias Bergentall, Malin E V Johansson, Gunnar C Hansson, Daniel J Drucker, Fredrik Bäckhed
OBJECTIVE: Theut microbiota increases energy availability through fermentation of dietary fibers to short-chain fatty acids in conventionally raised mice. Energy deficiency in germ-free (GF) mice increases glucagon-like peptide-1 (GLP-1) levels, which slows intestinal transit. To further analyze the role of GLP-1-mediated signaling in this model of energy deficiency, we re-derived mice lacking GLP-1 receptor (GLP-1R KO) as GF. METHODS: GLP-1R KO mice were rederived as GF through hysterectomy and monitored for 30 weeks...
March 21, 2024: Molecular Metabolism
#16
JOURNAL ARTICLE
Accessible luminal interface of bovine rectal organoids generated from cryopreserved biopsy tissues.
Minae Kawasaki, Yoko M Ambrosini
Developing precise species-specific in vitro models that closely resemble in vivo intestinal tissues is essential for advancing our understanding of gastrointestinal physiology and associated diseases. This is especially crucial in examining host-pathogen interactions, particularly in bovines, a known reservoir for microbes and pathogens posing substantial public health threats. This research investigated the viability of producing bovine rectal organoids from cryopreserved tissues. We compared two cryopreservation methods with a traditional technique using fresh tissues, evaluating their effectiveness through growth rates, long-term viability, and comprehensive structural, cellular, and genetic analyses...
2024: PloS One
#17
JOURNAL ARTICLE
Pang Lyu, Jinming Wen, Wenshuo Zhang, Ning Liu, Iris Stolzer, Andreas Gießl, Yewei Jia, Daniele Mauro, Fulin Zhang, Francesco Ciccia, Didier Soulat, Claudia Günther, Georg Schett, Aline Bozec
OBJECTIVES: To investigate the mechanism by which intestinal epithelial cell (IEC) death induces arthritis. METHODS: IEC death was assessed by staining for necroptosis and apoptosis markers and fluorescence in situ hybridisation at different time points during collagen-induced arthritis (CIA). During the development of CIA, messenger RNA (mRNA) sequencing was performed, followed by Gene Ontology enrichment analysis of differentially expressed genes. Mice deficient for hypoxia-inducible factor 1α ( Hif1a ) in IECs ( Hif1a ∆IEC ) were generated and induced for arthritis...
March 19, 2024: Annals of the Rheumatic Diseases
#18
JOURNAL ARTICLE
Milena Fronza Broering, Stefania Tocci, Noah T Sout, Chris Reutelingsperger, Sandra H P Farsky, Soumita Das, Ibrahim M Sayed
OBJECTIVE AND DESIGN: Annexin A1 (ANXA1) plays a role in maintaining intestinal hemostasis, especially following mucosal inflammation. The published data about ANXA1 was derived from experimental animal models where there is an overlapping between epithelial and immune cells. There is no in vitro gut epithelial model that can assess the direct effect of ANXA1 on the gut epithelium. METHODS: We developed high-throughput stem-cell-based murine epithelial cells and bacterial lipopolysaccharides (LPS) were used to induce inflammation...
March 18, 2024: Stem cell reviews and reports
#19
JOURNAL ARTICLE
Kei Miyakawa, Masakazu Machida, Tomoyuki Kawasaki, Masatoshi Kakizaki, Yayoi Kimura, Masaya Sugiyama, Hideki Hasegawa, Akihiro Umezawa, Hidenori Akutsu, Akihide Ryo
No abstract text is available yet for this article.
March 15, 2024: Cellular and Molecular Gastroenterology and Hepatology
#20
REVIEW
Anja Alicehajic, Annet Adriana Maria Duivenvoorden, Kaatje Lenaerts
Intestinal ischemia-reperfusion injury (IR) is implicated in various clinical conditions and causes damage to the intestinal epithelium resulting in intestinal barrier loss. This presents a substantial clinical challenge, emphasizing the importance of gaining a comprehensive understanding of molecular events to aid in the identification of novel therapeutic targets. This review systematically explores the extent to which omics technologies-transcriptomics, proteomics, metabolomics, and metagenomics-have already contributed to deciphering the molecular mechanisms contributing to intestinal IR injury, in in vivo and in vitro animal and human models, and in clinical samples...
March 13, 2024: Proteomics
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