Article
Multidisciplinary Sciences
Hung-Yu Chiang, Hsueh-Han Lu, Janaki N. Sudhakar, Yu-Wen Chen, Nien-Shin Shih, Yi-Ting Weng, Jr-Wen Shui
Summary: IL-22 induces IL-18 expression by intestinal epithelial cells, and IL-18 plays an important role in host defense against intestinal infection and inflammation.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Ying Li, Yudong Jiang, Lei Zhang, Wei Qian, Xiaohua Hou, Rong Lin
Summary: The study showed that exogenous l-fucose can protect intestinal barrier function and reduce the severity of colitis by increasing FUT2-mediated fucosylation of intestinal epithelial cells.
Article
Medicine, Research & Experimental
Lori Patnaude, Martha Mayo, Regina Mario, Xiaoming Wu, Heather Knight, Kelly Creamer, Sarah Wilson, Valerie Pivorunas, Jozsef Karman, Lucy Phillips, Robert Dunstan, Rajesh Kamath, Bradford McRae, Sonia Terrillon
Summary: The study found that IL-22 promotes expansion and proliferation of intestinal epithelial stem cells, as well as production of anti-microbial peptides. Additionally, IL-22 alters the composition of the mucus layer. However, the IL-22-associated epithelial phenotype differs in the presence of butyrate and immune cells.
Article
Multidisciplinary Sciences
Xingxing Li, Liuqing He, Jianhua Luo, Yangling Zheng, Yao Zhou, Danyang Li, Yuanyuan Zhang, Zhenrui Pan, Yanyan Li, Liang Tao
Summary: In this study, the importance of TMPRSS2 and surface fucosylation in the actions of Hemorrhagic toxin (TcsH) produced by Paeniclostridium sordellii was revealed. The authors carried out genome-wide screens and identified cell surface fucosylation and TMPRSS2 as host factors involved in the binding and entry of TcsH. It was found that TMPRSS2 and fucosylated glycans can independently mediate the binding/entry of TcsH, acting as redundant receptors. This study provides insights into the host recognition mechanisms for large clostridial toxins.
NATURE COMMUNICATIONS
(2022)
Article
Agriculture, Dairy & Animal Science
Min Zhu, Weiming Lai, Lewen Yao, E. Xu, Xiang Chen, Yi-yu Zhang, Xiang-Guang Li
Summary: The intestinal epithelium renews rapidly, and glutamine plays a crucial role in this process. This study aimed to identify the genes and signals involved in glutamine-induced growth of intestinal epithelial cells. The results showed that glutamine upregulates DNA replication licensing factors, leading to increased proliferation and suppressed inflammation pathways, resulting in the proliferation of porcine intestinal epithelial cells and expansion of intestinal stem cells.
Article
Cell Biology
Belgacem Mihi, Qingqing Gong, Lila S. Nolan, Sarah E. Gale, Martin Goree, Elise Hu, Wyatt E. Lanik, Jamie M. Rimer, Victoria Liu, Olivia B. Parks, Angela N. Lewis, Pranjal Agrawal, Marie L. Laury, Pawan Kumar, Elizabeth Huang, Shay S. Bidani, Cliff J. Luke, Jay K. Kolls, Misty Good
Summary: The lack of IL-22 production in neonates during NEC was found in both human and murine newborns, and the expression of II22 in the neonatal murine intestine is negligible until weaning. Treatment with recombinant IL-22 during NEC reduces inflammation and enhances epithelial regeneration, providing a potential new therapeutic strategy.
CELL REPORTS MEDICINE
(2021)
Article
Cell Biology
Yu Jiang, Zhongzhen Wang, Jinying Hu, Wei Wang, Na Zhang, Lili Gao
Summary: This study reveals that the modification of core fucosylation (CF) is associated with alveolar epithelial cells (AECs) senescence in pulmonary fibrosis. Inhibition of CF modification can attenuate AECs senescence and reduce pulmonary fibrosis.
Article
Immunology
Hideaki Fujiwara, Keisuke Seike, Michael D. Brooks, Anna Mathew, Ilya Kovalenko, Anupama Pal, Ho-Joon Lee, Daniel Peltier, Stephanie Kim, Chen Liu, Katherine Oravecz-Wilson, Lu Li, Yaping Sun, Jaeman Byun, Yoshinobu Maeda, Max S. Wicha, Tom Saunders, Alnawaz Rehemtulla, Costas A. Lyssiotis, Subramanian Pennarthur, Pavan Reddy
Summary: The alteration of IEC-specific mitochondrial complex II component SDHA plays a critical role in regulating the severity of T cell-mediated intestinal diseases, including graft-versus-host disease, inflammatory bowel disease and immune checkpoint blockade-mediated colitis.
Article
Microbiology
Ruyue Fan, Xiurui Han, Yanan Gong, Lihua He, Zhijing Xue, Yaming Yang, Lu Sun, Dongjie Fan, Yuanhai You, Fanliang Meng, Xiaomei Yan, Maojun Zhang, Jianzhong Zhang
Summary: The study investigated the expression of fucosylated glycans in gastric epithelial cells infected with H. pylori strains from patients with different diseases, and found that high levels of α 1,2-linked fucose synthesized by FUT1/2 may play a role in the preliminary stage of H. pylori infection.
Article
Immunology
Natalie Burkard, Michael Meir, Felix Kannapin, Christoph Otto, Maximilian Petzke, Christoph-Thomas Germer, Jens Waschke, Nicolas Schlegel
Summary: The study revealed that Dsg2 regulates the expression of Claudin2 by sequestering PI-3-kinase to the cell borders in intestinal epithelium. This interaction plays a critical role in maintaining intestinal epithelial barrier function and preventing inflammation-induced changes in tight junction proteins.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Gastroenterology & Hepatology
Haibo Yuan, Liting Zhou, Yilin Chen, Jiayi You, Hongye Hu, Yuanyuan Li, Rui Huang, Shuyan Wu
Summary: SopF, a newly discovered effector secreted by Salmonella pathogenicity island-1 type III secretion system (T3SS1), can attenuate intestinal inflammation and suppress IECs expulsion to promote bacterial dissemination in mice infected with Salmonella enterica serovar Typhimurium (S. Typhimurium). SopF activates phosphoinositide-dependent protein kinase-1 (PDK1) to phosphorylate p90 ribosomal S6 kinase (RSK), resulting in the down-regulation of Caspase-8 activation. Inactivation of Caspase-8 by SopF inhibits pyroptosis and apoptosis, but promotes necroptosis. The administration of PDK1 inhibitor AR-12 and RSK inhibitor BI-D1870 can overcome Caspase-8 blockade and counteract PANoptosis induced by SopF.
Article
Chemistry, Multidisciplinary
Yan-yang Li, Xiao-jing Wang, Yu-lin Su, Qing Wang, Shao-wei Huang, Zeng-feng Pan, Yan-ping Chen, Jun-jie Liang, Mei-ling Zhang, Xue-qian Xie, Zhi-yun Wu, Jin-yan Chen, Lian Zhou, Xia Luo
Summary: This study elucidates the molecular mechanisms underlying the protective effect of baicalein on intestinal barrier function in colitis mice, demonstrating that baicalein improves gut inflammation, reduces intestinal permeability, and restores tight junctions possibly via promoting AhR/IL-22 pathway. Co-administration of AhR antagonist CH223191 partially blocks the therapeutic effects of baicalein, while AhR agonist FICZ ameliorates symptoms and gut barrier function in colitis mice.
ACTA PHARMACOLOGICA SINICA
(2022)
Article
Cell & Tissue Engineering
Putianqi Wang, Noelyn Kljavin, Thi Thu Thao Nguyen, Elaine E. Storm, Bryan Marsh, Jian Jiang, William Lin, Hari Menon, Robert Piskol, Frederic J. de Sauvage
Summary: Neurons play a crucial role in regulating the regeneration of intestinal epithelial cells, as they stimulate the production of IL-22 from ILC3s to promote epithelial repair. This adrenergic-ILC3 axis is essential for intestinal regeneration.
Article
Plant Sciences
Hui Feng, Jiani Tan, Qijuan Wang, Tingting Zhou, Liu Li, Dongdong Sun, Minmin Fan, Haibo Cheng, Weixing Shen
Summary: This study found that silencing the SNX10 gene promotes cell proliferation and glucose metabolism activity in normal human intestinal epithelial cells. It was also discovered that a drug called alpha-hederin can reverse these effects by increasing the expression of the SNX10 gene, slowing down cell proliferation and glucose metabolism activity.
Article
Cell & Tissue Engineering
Ti-Dong Shan, Han Yue, Xue-Guo Sun, Yue-Ping Jiang, Li Chen
Summary: This study provides evidence of the essential role of Rspo3 in the differentiation of intestinal epithelial cells (IECs) in diabetes mellitus (DM). It was found that miR-380-5p regulates IEC differentiation by targeting Rspo3, suggesting potential therapeutic targets for diabetic enteropathy (DE).
STEM CELL RESEARCH & THERAPY
(2021)
Article
Multidisciplinary Sciences
Sydney Manning, Hung-Chih Ku, Douglas Dluzen, Chao Xing, Zhengyang Zhou
Summary: Identification of new genetic signals associated with susceptibility to complex human diseases is crucial for disease diagnosis, prevention, and treatment. This study compares the power of the Jonckheere-Terpstra (JT) trend test and the Cochran-Armitage (CA) trend test under different scenarios, and shows that the JT trend test outperforms the CA trend test in terms of statistical power in certain circumstances, especially when the sample size is small and the minor allele frequency is low. Overall, the JT trend test is a valuable alternative to the CA trend test for better detection of genetic signals and a finer understanding of their genetic architecture.
Article
Chemistry, Medicinal
Michael L. Neugent, Neha Hulyalkar, Ashwani Kumar, Chao Xing, Philippe E. Zimmern, Vladimir Shulaev, Nicole J. De Nisco
Summary: Glycosaminoglycans (GAGs) are linear polysaccharides with negative charges, composed of uronic acid and amino sugars. The bladder epithelium is covered by a layer of GAGs, which are believed to serve as a protective barrier and potential interaction site for the urinary microbiome. This study investigated urinary GAG composition in postmenopausal women and found that chondroitin sulfate (CS) is the major GAG. The study also identified an elevation of urinary CS in women with active recurrent urinary tract infection (rUTI). Additionally, the study revealed associations between urinary GAGs and urobiome composition, including specific bacterial species associated with different GAG types and vaginal dysbiosis.
ACS INFECTIOUS DISEASES
(2023)
Article
Biotechnology & Applied Microbiology
Kayvon Pedram, D. Judy Shon, Gabrielle S. Tender, Natalia R. Mantuano, Jason J. Northey, Kevin J. Metcalf, Simon P. Wisnovsky, Nicholas M. Riley, Giovanni C. Forcina, Stacy A. Malaker, Angel Kuo, Benson M. George, Caitlyn L. Miller, Kerriann M. Casey, Jose G. Vilches-Moure, Michael J. Ferracane, Valerie M. Weaver, Heinz Laeubli, Carolyn R. Bertozzi
Summary: Targeted protein degradation can suppress cancer in mice by eliminating undruggable proteins. In this study, degraders were designed to selectively degrade mucins, glycosylated proteins that drive cancer progression, by recognizing specific peptide and glycan motifs and binding to cell surfaces. The engineered protease, fused with a cancer antigen-binding nanobody, degraded mucins on cancer cells, induced cell death, and reduced tumor growth in mouse models of breast cancer. This research provides a blueprint for developing biologics that degrade specific protein glycoforms on target cells.
NATURE BIOTECHNOLOGY
(2023)
Article
Multidisciplinary Sciences
Joann Chongsaritsinsuk, Alexandra D. Steigmeyer, Keira E. Mahoney, Mia A. Rosenfeld, Taryn M. Lucas, Courtney M. Smith, Alice Li, Deniz Ince, Fiona L. Kearns, Alexandria S. Battison, Marie A. Hollenhorst, D. Judy Shon, Katherine H. Tiemeyer, Victor Attah, Catherine Kwon, Carolyn R. Bertozzi, Michael J. Ferracane, Mark A. Lemmon, Rommie E. Amaro, Stacy A. Malaker
Summary: This study investigates the structure and function of mucin glycoproteins. By using the mucinase SmE for mass spectrometric analysis, the researchers successfully overcome the challenges associated with studying mucin domains. They also employ molecular dynamics simulations and binding assays to gain a deeper understanding of how glycosylation controls protein structure and function.
NATURE COMMUNICATIONS
(2023)
Article
Genetics & Heredity
Widler Casy, Irvin T. Garza, Xin Chen, Thomas Dong, Yuhui Hu, Mohammed Kanchwala, Cynthia B. Trygg, Charles Shyng, Chao Xing, Bruce A. Bunnell, Stephen E. Braun, Steven J. Gray
Summary: The use of AAV capsid libraries with selection strategies has successfully generated novel AAVs with enhanced features. However, the inability to sequence the complete capsid gene in a high-throughput manner has limited capsid engineering. To overcome this limitation, AAV capsid shuffled libraries were generated and directed evolution was applied in mice and non-human primates to yield AAVs compatible for translational applications. The use of single molecule real-time sequencing and nuclei-enrichment step provided insights for variant identification in the central nervous system.
Article
Genetics & Heredity
Fieke W. Hoff, Chao Xing, Vinaya Simha, Anil K. Agarwal, Xunzhi Zhang, Leena Lekkala, Madhumati S. Vaishnav, Frank Vuitch, Abhimanyu Garg
Summary: Through a study on an Asian Indian family, it was found that 4 family members had Werner's syndrome instead of the common types of diabetes. The research suggests that the diagnosis of Werner's syndrome should be considered in cases with consanguinity, dysmorphic features, and malignancy.
MOLECULAR GENETICS & GENOMIC MEDICINE
(2023)
Article
Ophthalmology
Bogale Aredo, Ashwani Kumar, Bo Chen, Chao Xing, Rafael L. Ufret-Vincenty
Summary: In this study, the fundus camera-delivered light-induced retinal degeneration model was used to analyze cell type-specific responses to retinal oxidative injury. It was found that a subpopulation of Muller glia cells plays a crucial role in the cellular recovery process. These findings may contribute to the development of therapeutic approaches for minimizing damage and promoting recovery.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2023)
Article
Ophthalmology
Brian C. Leonard, Sangwan Park, Soohyun Kim, Laura J. Young, Iman Jalilian, Krista Cosert, Xunzhi Zhang, Jessica M. Skeie, Hanna Shevalye, Nayeli Echeverria, Vanessa Rozo, Xin Gong, Chao Xing, Christopher J. Murphy, Mark A. Greiner, V. Vinod Mootha, Vijay Krishna Raghunathan, Sara M. Thomasy
Summary: This study examines the role of Wwtr1 in murine ocular structure and function, and its relationship with FECD. The results suggest that Wwtr1 deficient mice exhibit phenotypic abnormalities similar to FECD-affected patients, indicating that they could serve as a murine model for late-onset FECD.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2023)
Article
Medicine, Research & Experimental
Chunhui Jiang, Ashwani Kumar, Ze Yu, Tracey Shipman, Yong Wang, Renee M. McKay, Chao Xing, Lu Q. Le
Summary: Neurofibromatosis type 1 (NF1) is a common tumor-predisposing genetic disorder characterized by the development of benign neurofibromas. This study explored the mechanism of extracellular matrix (ECM) deposition during neurofibroma development and treatment response. The researchers found that basement membrane (BM) proteins, rather than major collagen isoforms, were upregulated in the ECM during plexiform neurofibroma (pNF) development. They also identified TGF-β1 signaling as a key regulator of ECM dynamics and demonstrated that TGF-β1 overexpression promoted pNF progression. The findings suggest that BM proteins could serve as biomarkers for diagnosing and monitoring the treatment response of NF1.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Letter
Biochemistry & Molecular Biology
Michael Boyce, Stacy A. Malaker, Nicholas M. Riley, Jennifer J. Kohler
Article
Chemistry, Medicinal
Leah S. Imlay, Aloysus K. Lawong, Suraksha Gahalawat, Ashwani Kumar, Chao Xing, Nimisha Mittal, Sergio Wittlin, Alisje Churchyard, Hanspeter Niederstrasser, Benigno Crespo-Fernandez, Bruce A. Posner, Francisco-Javier Gamo, Jake Baum, Elizabeth A. Winzeler, Benoit Laleu, Joseph M. Ready, Margaret A. Phillips
Summary: Current malaria treatments face the threat of drug resistance, necessitating the development of new drugs. Through a screening process, (S)-SW228703 ((S)-SW703) was identified as a potential antimalarial with activity against asexual blood and liver stages and a fast-killing profile. Resistance to (S)-SW703 is associated with mutations in the Plasmodium falciparum cyclic amine resistance locus (Pf CARL) and P. falciparum acetyl CoA transporter (PfACT). The discovery of (S)-SW703 offers a new chemical series with broad activity for multiple life-cycle stages and a fast-killing mechanism, which can be further optimized for malaria treatment.
ACS INFECTIOUS DISEASES
(2023)
Article
Cell Biology
Islam Oguz Tuncay, Darlene Devries, Ashlesha Gogate, Kiran Kaur, Ashwani Kumar, Chao Xing, Kimberly Goodspeed, Leah Seyoum-Tesfa, Maria H. Chahrour
Summary: This study investigates the genetics of autism spectrum disorder (ASD) in an East African population, revealing a higher prevalence of ASD and decreased genetic heterogeneity. The findings highlight the importance of African genetic variation and admixture analysis in understanding the genetic architecture of complex disorders.
Article
Biochemistry & Molecular Biology
Akshi Singla, Andrew Boucher, Kerri-Lee Wallom, Michael Lebens, Jennifer J. Kohler, Frances M. Platt, Ulf Yrlid
Summary: Prior research on cholera toxin (CT) binding and intoxication has relied on human colonic cancer derived epithelial cells. However, this study used human enteroids derived from jejunal biopsies to study CT binding and intoxication of human non-transformed small intestinal epithelial cells. The study found that inhibition of fucosylation or O-glycosylation sensitized enteroids to CT intoxication. Furthermore, simultaneous inhibition of fucosylation and O-glycosylation increased the availability of additional glycoconjugates, but counteracted the sensitization in CT intoxication caused by inhibiting O-glycosylation due to reduction in fucose. This suggests a dual role of fucose in influencing CT binding and intoxication. Additionally, the study revealed a role for human genetic variation in determining sensitivity to CT.
Article
Medicine, Research & Experimental
Lei Bao, Ashwani Kumar, Ming Zhu, Yan Peng, Chao Xing, Jennifer E. Wang, Yingfei Wang, Weibo Luo
Summary: SAP30 is an important protein in breast cancer, and its upregulation is associated with unfavorable prognosis. Research has shown that SAP30 promotes tumor growth and metastasis through mechanisms other than canonical gene silencing. Additionally, SAP30 enhances cell motility, angiogenesis, and lymphangiogenesis by interacting with other proteins, thereby driving breast cancer progression.
JOURNAL OF CLINICAL INVESTIGATION
(2023)