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Das S, Konwar BK. The vital role of Lactobacillus sp. in vaginal health: Implications for enhanced prophylactic research. Probiotics Antimicrob Proteins 2025:10.1007/s12602-025-10574-7. [PMID: 40402415 DOI: 10.1007/s12602-025-10574-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/29/2025] [Indexed: 05/23/2025]
Abstract
Genital opening or vaginal canal (VC) in women has different embryological origin than the entire female reproductive system. The microenvironment of the VC post puberty is everchanging due to the hormonal fluctuations in a woman's body. However, the vaginal canal maintains a defined microbiota with higher population of inherent lactic acid bacteria (LAB) species under healthy conditions. The preservation of the beneficial flora in the genital area is dependent on genetic, social, and habitual factors. The understanding and practice of these factors prevents the commencement of various vaginal infections/vaginitis. Common vaginal infections have known antibiotic treatments; however, treatments of few infections are still unavailable. The study of sexual health is scarce in India due to social and economic factors, with less number of studies from various parts of the country. Thus, there is a necessity of new-age prophylactic solutions in such developing countries. This review highlights the origin of the female reproductive system and describes how the hormonal change initiates unique microenvironment development. Later, we have elaborately discussed the precautionary contribution of lactic acid bacteria and their unexplored commercial utilization, which in turn would help in various ways to improve the standards of reproductive hygiene products.
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Affiliation(s)
- Shreaya Das
- Dept. of Molecular Biology and Biotechnology, Tezpur University (Central), Napaam, 784028, Assam, India.
| | - Bolin Kumar Konwar
- Dept. of Molecular Biology and Biotechnology, Tezpur University (Central), Napaam, 784028, Assam, India
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Sugiyama Y, Konishi H, Dokoshi T, Tanaka H, Kobayashi Y, Sasaki T, Yamamoto K, Sakatani A, Takahashi K, Ando K, Ueno N, Kashima S, Moriichi K, Tanabe H, Okumura T, Fujiya M. hsa_circ_0015388 Reduces Macrophage Derived Reactive Oxygen Species in Crohn's Disease. Inflamm Bowel Dis 2025; 31:1355-1365. [PMID: 39807080 DOI: 10.1093/ibd/izae317] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2024] [Indexed: 01/16/2025]
Abstract
BACKGROUND Crohn's disease (CD) is a refractory inflammatory bowel disease with an unclear etiology. CircularRNA (circRNA) has been highlighted as a novel class of functional noncoding RNAs associated with the pathogenesis of various diseases. However, the functions of circRNA in CD remain unclear. METHODS Biopsies were obtained from noninflammatory sites in the terminal ileum of the CD group (n = 4) and non-CD group (n = 4) and analyzed for circRNA expression using RNA sequencing. The significantly altered circRNAs were validated in the CD group (n = 45) and non-CD group (n = 15) using quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Transcriptome analysis was conducted using circRNA-downregulated macrophage-like THP-1 cells. Reactive oxygen species (ROS) levels, cytokine mRNA expression, phagocytosis, and migration were evaluated in circRNA-downregulated THP-1 cells. RESULTS CircularRNA sequencing analysis revealed significant differences in 31 circRNAs between the CD group and non-CD group. Quantitative reverse transcriptase-polymerase chain reaction analysis for each circRNA demonstrated significant upregulation of hsa_circ_0015388 in the CD group. Hsa_circ_0015388 was expressed in THP-1 cells, but not in HCEC-1CT and Caco-2/bbe. Transcriptome analysis in THP-1 cells transfected with scramble or hsa_circ_0015388 siRNA (small interfering RNA) showed a significant alteration in innate immune response related pathway. Reactive oxygen species production was significantly increased in the hsa_circ_0015388 downregulated THP-1 cells. Reactive oxygen species induction in the hsa_circ_0015388 knocked down THP-1 was diminished by the inhibition of TNFSF10. CONCLUSION A comprehensive analysis of circRNA expression revealed that 31 circRNAs were dysregulated in the CD group. Hsa_circ_0015388 is expressed in macrophages and negatively regulates ROS function inhibiting the TNFSF10 pathway. This study first revealed that hsa_circ_0015388 plays a role in the pathogenesis of CD by suppressing ROS production in macrophages.
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Affiliation(s)
- Yuya Sugiyama
- Division of Metabolism and Biosystemic Science, Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Midorigaoka-Higashi 2-1-1-1, Asahikawa Hokkaido, 078-8510, Japan
| | - Hiroaki Konishi
- Department of Gastroenterology and Advanced Medical Sciences, Asahikawa Medical University, Midorigaoka-Higashi 2-1-1-1, Asahikawa Hokkaido, 078-8510, Japan
| | - Tatsuya Dokoshi
- Department of Dermatology, University of California San Diego, 9500 Gilman Dr, La Jolla, CA 92093, USA
| | - Hiroki Tanaka
- Division of Tumor Pathology, Department of Pathology, Asahikawa Medical University, Midorigaoka-Higashi 2-1-1-1, Asahikawa Hokkaido, 078-8510, Japan
| | - Yu Kobayashi
- Division of Metabolism and Biosystemic Science, Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Midorigaoka-Higashi 2-1-1-1, Asahikawa Hokkaido, 078-8510, Japan
| | - Takahiro Sasaki
- Division of Metabolism and Biosystemic Science, Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Midorigaoka-Higashi 2-1-1-1, Asahikawa Hokkaido, 078-8510, Japan
| | - Koji Yamamoto
- Department of Gastroenterology and Advanced Medical Sciences, Asahikawa Medical University, Midorigaoka-Higashi 2-1-1-1, Asahikawa Hokkaido, 078-8510, Japan
| | - Aki Sakatani
- Division of Metabolism and Biosystemic Science, Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Midorigaoka-Higashi 2-1-1-1, Asahikawa Hokkaido, 078-8510, Japan
| | - Keitaro Takahashi
- Division of Metabolism and Biosystemic Science, Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Midorigaoka-Higashi 2-1-1-1, Asahikawa Hokkaido, 078-8510, Japan
| | - Katsuyoshi Ando
- Division of Metabolism and Biosystemic Science, Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Midorigaoka-Higashi 2-1-1-1, Asahikawa Hokkaido, 078-8510, Japan
| | - Nobuhiro Ueno
- Division of Metabolism and Biosystemic Science, Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Midorigaoka-Higashi 2-1-1-1, Asahikawa Hokkaido, 078-8510, Japan
| | - Shin Kashima
- Division of Metabolism and Biosystemic Science, Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Midorigaoka-Higashi 2-1-1-1, Asahikawa Hokkaido, 078-8510, Japan
| | - Kentaro Moriichi
- Division of Metabolism and Biosystemic Science, Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Midorigaoka-Higashi 2-1-1-1, Asahikawa Hokkaido, 078-8510, Japan
| | - Hiroki Tanabe
- Division of Metabolism and Biosystemic Science, Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Midorigaoka-Higashi 2-1-1-1, Asahikawa Hokkaido, 078-8510, Japan
| | - Toshikatsu Okumura
- Division of Metabolism and Biosystemic Science, Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Midorigaoka-Higashi 2-1-1-1, Asahikawa Hokkaido, 078-8510, Japan
| | - Mikihiro Fujiya
- Division of Metabolism and Biosystemic Science, Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Midorigaoka-Higashi 2-1-1-1, Asahikawa Hokkaido, 078-8510, Japan
- Department of Gastroenterology and Advanced Medical Sciences, Asahikawa Medical University, Midorigaoka-Higashi 2-1-1-1, Asahikawa Hokkaido, 078-8510, Japan
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Li J, Wang L, Wang M, Zhang H. Activation of aryl hydrocarbon receptor attenuates intestinal inflammation by enhancing IRF4-mediated macrophage M2 polarization. Biochim Biophys Acta Mol Basis Dis 2025; 1871:167735. [PMID: 39971258 DOI: 10.1016/j.bbadis.2025.167735] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2024] [Revised: 01/16/2025] [Accepted: 02/14/2025] [Indexed: 02/21/2025]
Abstract
BACKGROUND Crohn's disease (CD) is characterized by immune cell dysregulation, with macrophages playing an indisputable role. Macrophages can exhibit opposing polarization under different conditions, resulting in pro- or anti-inflammatory effects. The aryl hydrocarbon receptor (AhR), a ligand-dependent transcription factor, is implicated in intestinal inflammation by regulating both innate and adaptive immune responses. However, the regulatory mechanism between AhR and macrophages in colitis has not been thoroughly investigated. METHODS Macrophage polarization in the colonic tissue of active CD patients was assessed. Following colitis induction in mice by 2,4,6-trinitro-benzenesulfonic acid (TNBS), an intraperitoneal injection of the natural AhR agonist 6-formylindolo[3,2-b]carbazole (FICZ) was administered. The severity of colitis was estimated, and macrophage polarization was detected. In an in vitro setting, bone marrow-derived macrophages (BMDMs) were polarized to the M2 phenotype in the presence or absence of FICZ. Interferon regulatory factor 4 (IRF4) siRNA was applied to knockdown IRF4 expression. M2-specific markers were quantified using quantitative real-time PCR (qRT-PCR), enzyme-linked immunosorbent assay (ELISA) and flow cytometry. RESULTS Compared with healthy controls, active CD patients exhibited a lower presence of M2 macrophages in colonic tissue. Experimentally, FICZ was found to protect mice against TNBS-induced colitis, as evidenced by reduced diarrhea, bloody stool, and weight loss. This effect was associated with an increase in M2 macrophages and the release of IL-10 in the intestine. In BMDMs, FICZ promoted the expressions of M2-specific markers, including Ym1, Fizz1, IL-10, and CD206. Furthermore, FICZ upregulated IRF4 expression. After IRF4 silencing with siRNA, the enhancement of macrophage M2 polarization by FICZ was significantly impaired. CONCLUSION Activation of AhR appears to have a beneficial effect on intestinal inflammation by promoting macrophage M2 polarization. This effect is partially mediated by the upregulation of IRF4 expression and may lead to new insight into the pathogenesis of CD.
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Affiliation(s)
- Jiajia Li
- Department of Gastroenterology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Lu Wang
- Department of Gastroenterology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Mingyuan Wang
- Department of Gastroenterology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Hongjie Zhang
- Department of Gastroenterology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
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Nienaber-Rousseau C. Understanding and applying gene-environment interactions: a guide for nutrition professionals with an emphasis on integration in African research settings. Nutr Rev 2025; 83:e443-e463. [PMID: 38442341 PMCID: PMC11723160 DOI: 10.1093/nutrit/nuae015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/07/2024] Open
Abstract
Noncommunicable diseases (NCDs) are influenced by the interplay between genetics and environmental exposures, particularly diet. However, many healthcare professionals, including nutritionists and dietitians, have limited genetic background and, therefore, they may lack understanding of gene-environment interactions (GxEs) studies. Even researchers deeply involved in nutrition studies, but with a focus elsewhere, can struggle to interpret, evaluate, and conduct GxE studies. There is an urgent need to study African populations that bear a heavy burden of NCDs, demonstrate unique genetic variability, and have cultural practices resulting in distinctive environmental exposures compared with Europeans or Americans, who are studied more. Although diverse and rapidly changing environments, as well as the high genetic variability of Africans and difference in linkage disequilibrium (ie, certain gene variants are inherited together more often than expected by chance), provide unparalleled potential to investigate the omics fields, only a small percentage of studies come from Africa. Furthermore, research evidence lags behind the practices of companies offering genetic testing for personalized medicine and nutrition. We need to generate more evidence on GxEs that also considers continental African populations to be able to prevent unethical practices and enable tailored treatments. This review aims to introduce nutrition professionals to genetics terms and valid methods to investigate GxEs and their challenges, and proposes ways to improve quality and reproducibility. The review also provides insight into the potential contributions of nutrigenetics and nutrigenomics to the healthcare sphere, addresses direct-to-consumer genetic testing, and concludes by offering insights into the field's future, including advanced technologies like artificial intelligence and machine learning.
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Affiliation(s)
- Cornelie Nienaber-Rousseau
- Centre of Excellence for Nutrition, North-West University, Potchefstroom, South Africa
- SAMRC Extramural Unit for Hypertension and Cardiovascular Disease, Faculty of Health Sciences, North-West University, Potchefstroom, South Africa
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Li JH, Xu J, Huang C, Hu JX, Xu HM, Guo X, Zhang Y, Xu JK, Peng Y, Zhang Y, Zhu MZ, Zhou YL, Nie YQ. Houttuynia cordata-Derived Exosome-Like Nanoparticles Mitigate Colitis in Mice via Inhibition of the NLRP3 Signaling Pathway and Modulation of the Gut Microbiota. Int J Nanomedicine 2024; 19:13991-14018. [PMID: 39742094 PMCID: PMC11687308 DOI: 10.2147/ijn.s493434] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2024] [Accepted: 12/19/2024] [Indexed: 01/03/2025] Open
Abstract
BACKGROUND Plant-derived exosome-like nanoparticles (PELNs) have received widespread attention in treating ulcerative colitis (UC). However, the role of Houttuynia cordata-derived exosome-like nanoparticles (HELNs) in UC remains unclear. This study aims to evaluate the efficacy of HELNs in treating colitis in mice and investigate its potential mechanisms. METHODS HELNs were isolated from H. cordata for characterization, and their safety and stability were evaluated. A dextran sulfate sodium (DSS)-induced colitis mouse model was utilized to assess the therapeutic potential of HELNs in UC. In vivo, imaging and flow cytometry were utilized to investigate the targeting effect of HELNs on inflamed colonic sites and their modulation of the immune environment. RNA-seq analysis and molecular docking were performed to identify potential pathways recruited by HELNs. Guided by transcriptomic findings, NLRP3-/- mice were used in conjunction with Western blotting, qPCR, immunofluorescence, and other techniques to verify that HELNs alleviated DSS-induced colitis by inhibiting NLRP3/NOD-like receptor signaling pathways. Lastly, the impact of HELNs on the gut microbiota was investigated through 16S rRNA sequencing. RESULTS HELNs significantly reduced the severity of DSS-induced colitis in mice, alleviating colitis symptoms and histopathological damage. Furthermore, HELNs can specifically target inflamed colon tissue, regulate the immune environment, and decrease inflammation. RNA-seq analysis, coupled with the use of NLRP3-/- mice, demonstrated that HELNs inhibited the NLRP3/NOD-like receptor signaling pathways. Lastly, HELNs balanced the gut microbiota composition in mice with colitis, decreasing the abundance of harmful bacteria and increasing the abundance of beneficial bacteria in the intestinal tract of these mice. CONCLUSION In summary, HELNs exhibit the potential to protect the colon from DSS-induced damage by inhibiting the NLRP3/NOD-like receptor signaling pathway and modulating the gut microbiota, presenting a promising therapeutic option for the management of UC.
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Affiliation(s)
- Jian-Hong Li
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, People’s Republic of China
- Department of Gastroenterology and Hepatology, Guangzhou First People’s Hospital, South China University of Technology, Guangzhou, Guangdong, People’s Republic of China
| | - Jing Xu
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, People’s Republic of China
- Department of Gastroenterology and Hepatology, Guangzhou First People’s Hospital, South China University of Technology, Guangzhou, Guangdong, People’s Republic of China
| | - Chen Huang
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, People’s Republic of China
- Department of Gastroenterology and Hepatology, Guangzhou First People’s Hospital, South China University of Technology, Guangzhou, Guangdong, People’s Republic of China
| | - Jin-Xia Hu
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, People’s Republic of China
- Department of Gastroenterology and Hepatology, Guangzhou First People’s Hospital, South China University of Technology, Guangzhou, Guangdong, People’s Republic of China
| | - Hao-Ming Xu
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, People’s Republic of China
- Department of Gastroenterology and Hepatology, Guangzhou First People’s Hospital, South China University of Technology, Guangzhou, Guangdong, People’s Republic of China
| | - Xue Guo
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, People’s Republic of China
- Department of Gastroenterology and Hepatology, Guangzhou First People’s Hospital, South China University of Technology, Guangzhou, Guangdong, People’s Republic of China
| | - Yan Zhang
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, People’s Republic of China
- Department of Gastroenterology and Hepatology, Guangzhou First People’s Hospital, South China University of Technology, Guangzhou, Guangdong, People’s Republic of China
| | - Jing-Kui Xu
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, People’s Republic of China
- Department of Gastroenterology and Hepatology, Guangzhou First People’s Hospital, South China University of Technology, Guangzhou, Guangdong, People’s Republic of China
| | - Yao Peng
- Department of Gastroenterology and Hepatology, Shenzhen General Hospital, Shenzhen, People’s Republic of China
| | - Yong Zhang
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, People’s Republic of China
- Department of Gastroenterology and Hepatology, Guangzhou First People’s Hospital, South China University of Technology, Guangzhou, Guangdong, People’s Republic of China
| | - Min-Zheng Zhu
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, People’s Republic of China
- Department of Gastroenterology and Hepatology, Guangzhou First People’s Hospital, South China University of Technology, Guangzhou, Guangdong, People’s Republic of China
| | - You-Lian Zhou
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, People’s Republic of China
- Department of Gastroenterology and Hepatology, Guangzhou First People’s Hospital, South China University of Technology, Guangzhou, Guangdong, People’s Republic of China
| | - Yu-Qiang Nie
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, People’s Republic of China
- Department of Gastroenterology and Hepatology, Guangzhou First People’s Hospital, South China University of Technology, Guangzhou, Guangdong, People’s Republic of China
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Zhao Y, Zhu S, Dong Y, Xie T, Chai Z, Gao X, Dai Y, Wang X. The Role of Gut Microbiome in Irritable Bowel Syndrome: Implications for Clinical Therapeutics. Biomolecules 2024; 14:1643. [PMID: 39766350 PMCID: PMC11674646 DOI: 10.3390/biom14121643] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2024] [Revised: 12/12/2024] [Accepted: 12/19/2024] [Indexed: 01/11/2025] Open
Abstract
Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder (FGID) characterized by chronic or recurrent gastrointestinal symptoms without organic changes, and it is also a common disorder of gut-brain interaction (DGBIs).. The symptoms of IBS not only affect the quality of life for individual patients but also place a significant burden on global healthcare systems. The lack of established and universally applicable biomarkers for IBS, along with the substantial variability in symptoms and progression, presents challenges in developing effective clinical treatments. In recent years, preclinical and clinical studies have linked the pathogenesis of IBS to alterations in the composition and function of the intestinal microbiota. Within the complex microbial community of the gut, intricate metabolic and spatial interactions occur among its members and between microbes and their hosts. Amid the multifaceted pathophysiology of IBS, the role of intestinal microenvironment factors in symptom development has become more apparent. This review aims to delve into the changes in the composition and structure of the gut microbiome in individuals with IBS. It explores how diet-mediated alterations in intestinal microbes and their byproducts play a role in regulating the pathogenesis of IBS by influencing the "brain-gut" axis, intestinal barrier function, immune responses, and more. By doing so, this review seeks to lay a theoretical foundation for advancing the development of clinical therapeutics for IBS.
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Affiliation(s)
- Yucui Zhao
- Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; (Y.Z.); (S.Z.); (Y.D.); (T.X.); (Z.C.); (X.G.)
- School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
- State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
| | - Shixiao Zhu
- Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; (Y.Z.); (S.Z.); (Y.D.); (T.X.); (Z.C.); (X.G.)
- School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
- State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
| | - Yingling Dong
- Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; (Y.Z.); (S.Z.); (Y.D.); (T.X.); (Z.C.); (X.G.)
- School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
- State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
| | - Tian Xie
- Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; (Y.Z.); (S.Z.); (Y.D.); (T.X.); (Z.C.); (X.G.)
- School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
- State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
| | - Zhiqiang Chai
- Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; (Y.Z.); (S.Z.); (Y.D.); (T.X.); (Z.C.); (X.G.)
- School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
- State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
| | - Xiumei Gao
- Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; (Y.Z.); (S.Z.); (Y.D.); (T.X.); (Z.C.); (X.G.)
| | - Yongna Dai
- Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; (Y.Z.); (S.Z.); (Y.D.); (T.X.); (Z.C.); (X.G.)
| | - Xiaoying Wang
- Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; (Y.Z.); (S.Z.); (Y.D.); (T.X.); (Z.C.); (X.G.)
- School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
- State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
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Shen Y, Shi R, Lu S, Wang Y, Zhou Z, Wu C, You Q, Fan H, Wu J. Role of Peptidyl Arginine Deiminase 4-Dependent Macrophage Extracellular Trap Formation in Type 1 Diabetes Pathogenesis. Diabetes 2024; 73:1862-1874. [PMID: 39137121 DOI: 10.2337/db23-1000] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2023] [Accepted: 08/06/2024] [Indexed: 08/15/2024]
Abstract
Excessive formation of macrophage extracellular trap (MET) has been implicated in several autoimmune disease pathogeneses; however, its impact on type 1 diabetes (T1D) and related mechanisms remains enigmatic. We demonstrated the pivotal role of peptidyl arginine deiminase 4 (PAD4) in driving profuse MET formation and macrophage M1 polarization in intestinal inflammation in NOD mice. Genetic knockout of PAD4 or adoptive transfer of METs altered the proportion of proinflammatory T cells in the intestine, subsequently influencing their migration to the pancreas. Combining RNA sequencing and CUT&Tag analysis, we found activated PAD4 transcriptionally regulated CXCL10 expression. This study comprehensively investigated how excessive PAD4-mediated MET formation in the colon increases the aggravation of intestinal inflammation and proinflammatory T-cell migration and finally is involved in T1D progression, suggesting that inhibition of MET formation may be a potential therapeutic target in T1D. ARTICLE HIGHLIGHTS
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Affiliation(s)
- Yiming Shen
- School of Life Science and Technology, China Pharmaceutical University, Nanjing, China
| | - Ruiya Shi
- School of Life Science and Technology, China Pharmaceutical University, Nanjing, China
| | - ShiPing Lu
- Center for Translational Research in Infection and Inflammation, Tulane University, New Orleans, LA
| | - Yan Wang
- School of Life Science and Technology, China Pharmaceutical University, Nanjing, China
| | - Ziqi Zhou
- School of Life Science and Technology, China Pharmaceutical University, Nanjing, China
| | - Chenhua Wu
- School of Life Science and Technology, China Pharmaceutical University, Nanjing, China
| | - Qi You
- School of Life Science and Technology, China Pharmaceutical University, Nanjing, China
| | - Hongye Fan
- School of Life Science and Technology, China Pharmaceutical University, Nanjing, China
| | - Jie Wu
- School of Life Science and Technology, China Pharmaceutical University, Nanjing, China
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Yang Z, Zhang H, Yuan Z, Chen J, Zheng G, Zou S. The effects of GCRV on various tissues of grass carp (Ctenopharyngodon idella) and identification of differential interferon-stimulating genes (ISGs) through muscle transcriptome analysis. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2024; 284:116956. [PMID: 39208574 DOI: 10.1016/j.ecoenv.2024.116956] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/23/2024] [Revised: 08/24/2024] [Accepted: 08/25/2024] [Indexed: 09/04/2024]
Abstract
Grass carp hemorrhagic disease is caused by the grass carp reovirus (GCRV). The disease spreads rapidly and has a high fatality rate, which seriously affects grass carp culture. Moreover, the molecular mechanisms underlying grass carp hemorrhagic disease remain unclear. To decipher the effects of GCRV on grass carp tissues, resistant grass carp A (GA) and susceptible grass carp B (GB) were selected through GCRV treatment, and control grass carp C (GC) was also established. The gill, liver, and muscle tissues exhibited different onset symptoms under the influence of GCRV by histological observation. We selected muscle samples with significant differences in symptoms for Illumina RNA sequencing. Analyses using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes revealed 3512, 3074, and 1853 differentially expressed genes between "GC vs. GB," "GC vs. GA," and "GA vs. GB," respectively. Additionally, 40 differential immune-related genes and 28 differential interferon-stimulating genes (ISGs) related to the interferon (IFN) pathway were identified. The expression of immunogene-related genes of GB and GA, such as MDA5, IL-34, NF-KB, TRIM25, SOCS3, CEBPB, and BCL2, and genes associated with the JAK-STAT signaling pathway, such as IRF4, STAT1, STAT3, JAK 1, and JAK 2, was significantly upregulated. The IFN and JAK-STAT signaling pathways were closely related to anti-GCRV infection. The transcriptome data and predicted immune genes and ISGs in this study provide novel insights into the treatment of GCRV.
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Affiliation(s)
- Ziquan Yang
- Key Laboratory of Freshwater Aquatic Genetic Resources, Ministry of Agriculture and Rural Affairs, Shanghai Ocean University, Shanghai 201306, China; Genetics and Breeding Center for Blunt Snout Bream, Ministry of Agriculture and Rural Affairs, Shanghai Ocean University, Shanghai 201306, China
| | - Huimei Zhang
- Key Laboratory of Freshwater Aquatic Genetic Resources, Ministry of Agriculture and Rural Affairs, Shanghai Ocean University, Shanghai 201306, China; Genetics and Breeding Center for Blunt Snout Bream, Ministry of Agriculture and Rural Affairs, Shanghai Ocean University, Shanghai 201306, China
| | - Ziming Yuan
- Key Laboratory of Freshwater Aquatic Genetic Resources, Ministry of Agriculture and Rural Affairs, Shanghai Ocean University, Shanghai 201306, China; Genetics and Breeding Center for Blunt Snout Bream, Ministry of Agriculture and Rural Affairs, Shanghai Ocean University, Shanghai 201306, China
| | - Jie Chen
- Key Laboratory of Freshwater Aquatic Genetic Resources, Ministry of Agriculture and Rural Affairs, Shanghai Ocean University, Shanghai 201306, China; Genetics and Breeding Center for Blunt Snout Bream, Ministry of Agriculture and Rural Affairs, Shanghai Ocean University, Shanghai 201306, China; National Demonstration Center for Experimental Fisheries Science Education, Shanghai Ocean University, Shanghai 201306, China
| | - Guodong Zheng
- Key Laboratory of Freshwater Aquatic Genetic Resources, Ministry of Agriculture and Rural Affairs, Shanghai Ocean University, Shanghai 201306, China; Genetics and Breeding Center for Blunt Snout Bream, Ministry of Agriculture and Rural Affairs, Shanghai Ocean University, Shanghai 201306, China; National Demonstration Center for Experimental Fisheries Science Education, Shanghai Ocean University, Shanghai 201306, China.
| | - Shuming Zou
- Key Laboratory of Freshwater Aquatic Genetic Resources, Ministry of Agriculture and Rural Affairs, Shanghai Ocean University, Shanghai 201306, China; Genetics and Breeding Center for Blunt Snout Bream, Ministry of Agriculture and Rural Affairs, Shanghai Ocean University, Shanghai 201306, China; National Demonstration Center for Experimental Fisheries Science Education, Shanghai Ocean University, Shanghai 201306, China.
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9
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Chung YC, Lee A, Jang CH, Ryuk JA, Ha H, Hwang YH. Isatidis Folium Represses Dextran Sulfate Sodium-Induced Colitis and Suppresses the Inflammatory Response by Inhibiting Inflammasome Activation. Nutrients 2024; 16:3323. [PMID: 39408295 PMCID: PMC11478736 DOI: 10.3390/nu16193323] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2024] [Revised: 09/19/2024] [Accepted: 09/26/2024] [Indexed: 10/20/2024] Open
Abstract
BACKGROUND/OBJECTIVES Isatidis Folium (IF) has been used in traditional medicine for various ailments, and recent research highlights its anti-inflammatory, antiviral, and detoxifying properties. This study investigated the anti-inflammatory effects of a hydroethanolic extract of IF (EIF) on inflammasomes and colitis. METHODS Dextran sulfate sodium (DSS)-induced colitis model C57BL/6 mice were treated with DSS, mesalamine, or EIF (200 mg/kg). Parameters such as daily disease activity index (DAI), spleen weight, colon length, and histopathology were evaluated. Intestinal fibrosis, mucin, and tight junction proteins were assessed using Masson's trichrome, periodic acid-Schiff, and immunohistochemistry staining. RAW264.7 and J774a.1 macrophages were treated with EIF and lipopolysaccharide, with cell viability assessed via the cell counting kit-8 assay, nitric oxide (NO) production with Griess reagent, and cytokine levels with the enzyme-linked immunosorbent assay. NF-κB inhibition was analyzed using the luciferase assay, and phytochemical analysis was performed using UPLC-MS/MS. RESULTS EIF mitigated weight loss, reduced DAI scores, prevented colon shortening, and attenuated mucosal damage, fibrosis, and goblet cell loss while enhancing the tight junction protein occludin. The anti-inflammatory effects of EIF in RAW264.7 cells included reduced NO production, pro-inflammatory cytokines, and NF-κB activity, along with inhibition of NLRP3 inflammasome responses in J774a.1 cells. The key constituents identified were tryptanthrin, indigo, and indirubin. CONCLUSIONS Animal studies demonstrated the efficacy of EIF in alleviating colitis, suggesting its potential for treating inflammatory diseases.
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Affiliation(s)
- You Chul Chung
- KM Convergence Research Division, Korea Institution of Oriental Medicine, 1672 Yuseong-daero, Yuseong-gu, Daejeon 34054, Republic of Korea; (Y.C.C.); (A.L.); (C.H.J.); (J.A.R.); (H.H.)
| | - Ami Lee
- KM Convergence Research Division, Korea Institution of Oriental Medicine, 1672 Yuseong-daero, Yuseong-gu, Daejeon 34054, Republic of Korea; (Y.C.C.); (A.L.); (C.H.J.); (J.A.R.); (H.H.)
- Korean Convergence Medical Science Major, KIOM School, University of Science & Technology (UST), Daejeon 34054, Republic of Korea
| | - Chan Ho Jang
- KM Convergence Research Division, Korea Institution of Oriental Medicine, 1672 Yuseong-daero, Yuseong-gu, Daejeon 34054, Republic of Korea; (Y.C.C.); (A.L.); (C.H.J.); (J.A.R.); (H.H.)
| | - Jin Ah Ryuk
- KM Convergence Research Division, Korea Institution of Oriental Medicine, 1672 Yuseong-daero, Yuseong-gu, Daejeon 34054, Republic of Korea; (Y.C.C.); (A.L.); (C.H.J.); (J.A.R.); (H.H.)
| | - Hyunil Ha
- KM Convergence Research Division, Korea Institution of Oriental Medicine, 1672 Yuseong-daero, Yuseong-gu, Daejeon 34054, Republic of Korea; (Y.C.C.); (A.L.); (C.H.J.); (J.A.R.); (H.H.)
| | - Youn-Hwan Hwang
- KM Convergence Research Division, Korea Institution of Oriental Medicine, 1672 Yuseong-daero, Yuseong-gu, Daejeon 34054, Republic of Korea; (Y.C.C.); (A.L.); (C.H.J.); (J.A.R.); (H.H.)
- Korean Convergence Medical Science Major, KIOM School, University of Science & Technology (UST), Daejeon 34054, Republic of Korea
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10
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Tang J, Wang Q, Yu H, Dong L, Tang M, Arif A, Zhang G, Zhang T, Xie K, Su S, Zhao Z, Dai G. A Comparison of the Cecal Microbiota between the Infection and Recovery Periods in Chickens with Different Susceptibilities to Eimeria tenella. Animals (Basel) 2024; 14:2709. [PMID: 39335298 PMCID: PMC11428751 DOI: 10.3390/ani14182709] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2024] [Revised: 09/04/2024] [Accepted: 09/16/2024] [Indexed: 09/30/2024] Open
Abstract
To investigate the effect of Eimeria tenella (E. tenella) infection on the cecal microbiota, resistant and susceptible families were screened out based on the coccidiosis resistance evaluation indexes after E. tenella infection. Subsequently, a comparative analysis of cecal microorganisms among control, resistant, and susceptible groups as well as between different periods following the E. tenella challenge was conducted using metagenomic sequencing technology. The results showed that the abundance of opportunistic pathogens, such as Pantoea, Sporomusa, and Pasteurella in the susceptible group and Helicobacter and Sutterella in the resistant group, was significantly higher on day 27 post-inoculation (PI) (the recovery period) than on day 5 PI (the infection period). Additionally, the abundance of Alistipes, Butyricicoccus, and Eubacterium in the susceptible group and Coprococcus, Roseburia, Butyricicoccus, and Lactobacillus in the resistant group showed a significant upward trend during the infection period compared with that in the recovery period. On day 5 PI, the abundance of Faecalibacterium and Lactobacillus was decreased in both the resistant and susceptible groups when compared with that in the control group and was greater in the resistant group than in the susceptible group, while Alistipes in the susceptible group had a relatively higher abundance than that in other groups. A total of 49 biomarker taxa were identified using the linear discriminant analysis (LDA) effect size (LEfSe) method. Of these, the relative abundance of Lactobacillus aviarius, Lactobacillus salivarius, Roseburia, and Ruminococcus gauvreauii was increased in the resistant group, while Bacteroides_sp__AGMB03916, Fusobacterium_mortiferum, Alistipes_sp__An31A, and Alistipes_sp__Marseille_P5061 were enriched in the susceptible group. On day 27 PI, LDA scores identified 43 biomarkers, among which the relative abundance of Elusimicrobium_sp__An273 and Desulfovibrio_sp__An276 was increased in the resistant group, while that of Bacteroides_sp__43_108, Chlamydiia, Chlamydiales, and Sutterella_sp__AM11 39 was augmented in the susceptible group. Our results indicated that E. tenella infection affects the structure of the cecal microbiota during both the challenge and recovery periods. These findings will enhance the understanding of the effects of changes in the cecal microbiota on chickens after coccidia infection and provide a reference for further research on the mechanisms underlying how the intestinal microbiota influence the growth and health of chickens.
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Affiliation(s)
- Jianqiang Tang
- College of Animal Science and Technology, Yangzhou University, Yangzhou 225000, China
| | - Qi Wang
- College of Animal Science and Technology, Yangzhou University, Yangzhou 225000, China
| | - Hailiang Yu
- College of Animal Science and Technology, Yangzhou University, Yangzhou 225000, China
| | - Liyue Dong
- College of Animal Science and Technology, Yangzhou University, Yangzhou 225000, China
| | - Meihui Tang
- College of Animal Science and Technology, Yangzhou University, Yangzhou 225000, China
| | - Areej Arif
- College of Animal Science and Technology, Yangzhou University, Yangzhou 225000, China
| | - Genxi Zhang
- College of Animal Science and Technology, Yangzhou University, Yangzhou 225000, China
| | - Tao Zhang
- College of Animal Science and Technology, Yangzhou University, Yangzhou 225000, China
| | - Kaizhou Xie
- College of Animal Science and Technology, Yangzhou University, Yangzhou 225000, China
| | - Shijie Su
- College of Animal Science and Technology, Yangzhou University, Yangzhou 225000, China
| | - Zhenhua Zhao
- Poultry Institute, Chinese Academy of Agricultural Sciences, Yangzhou 225125, China
| | - Guojun Dai
- College of Animal Science and Technology, Yangzhou University, Yangzhou 225000, China
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11
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Chen R, Li C, Zheng J, Fan Z, Li L, Chen M, Chen B, Zhang S. Lymphocyte subsets for predicting inflammatory bowel disease progression and treatment response: a systematic review. Front Immunol 2024; 15:1403420. [PMID: 39229260 PMCID: PMC11368782 DOI: 10.3389/fimmu.2024.1403420] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2024] [Accepted: 08/05/2024] [Indexed: 09/05/2024] Open
Abstract
Background Lymphocytes play a key role in the pathogenesis of inflammatory bowel disease (IBD) and are widely explored as promising prognostic indicators. We aimed to outline the existing evidences on the capability of lymphocyte subpopulations to predict disease progression and treatment response in patients with IBD. Methods The protocol for this review was registered in PROSPERO (registration ID: CRD 42022364126). Systematic retrieval was conducted using PubMed, Embase, and Web of Science databases. Original articles on the prognostic value of lymphocyte subsets in IBD published up to April 8, 2023 were eligible for inclusion. The Newcastle-Ottawa Scale was used to evaluate the risk of bias. Results Twenty studies were ultimately included: eight evaluated the prediction of disease progression and 12 focused on the prediction of treatment response. According to the Newcastle-Ottawa Scale, three studies were of high quality, 16 were of moderate quality, and only one was of low quality. T-cell subpopulations, including CD4+ T cells, CD8+ T cells, and γδ T cells, are revealed to have prognostic capacity. Transmembrane tumor necrosis factor α-bearing lymphocytes, CD4+ T cells, CD8+ T cells, and Plasma cells are found to have the potential to predict the response to anti-TNFα agents. In contrast memory T cells, CD4+ T cells, and naïve B cells may predict the response to vedolizumab. Conclusions This systematic review identified several potential lymphocyte subset-related predictors. If verified in large cohort prospective studies, these findings could aid clinical decision-making. Systematic Review Registration https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022364126.
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Affiliation(s)
- Rirong Chen
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Chao Li
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Department of Clinical Medicine, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China
| | - Jieqi Zheng
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Department of Clinical Medicine, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China
| | - Zinan Fan
- Department of Clinical Medicine, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China
| | - Li Li
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Minhu Chen
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Baili Chen
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Shenghong Zhang
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Guangxi Hospital Division of The First Affiliated Hospital, Sun Yat-sen University, Nanning, China
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12
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Melhem H, Niess JH. Eosinophilic Esophagitis and Inflammatory Bowel Disease: What Are the Differences? Int J Mol Sci 2024; 25:8534. [PMID: 39126102 PMCID: PMC11313654 DOI: 10.3390/ijms25158534] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2024] [Revised: 07/19/2024] [Accepted: 07/20/2024] [Indexed: 08/12/2024] Open
Abstract
Eosinophilic esophagitis (EoE) and inflammatory bowel disease (IBD) are chronic inflammatory disorders of the gastrointestinal tract, with EoE predominantly provoked by food and aeroallergens, whereas IBD is driven by a broader spectrum of immunopathological and environmental triggers. This review presents a comprehensive comparison of the pathophysiological and therapeutic strategies for EoE and IBD. We examine the current understanding of their underlying mechanisms, particularly the interplay between environmental factors and genetic susceptibility. A crucial element in both diseases is the integrity of the epithelial barrier, whose disruption plays a central role in their pathogenesis. The involvement of eosinophils, mast cells, B cells, T cells, dendritic cells, macrophages, and their associated cytokines is examined, highlighting the importance of targeting cytokine signaling pathways to modulate immune-epithelial interactions. We propose that advances in computation tools will uncover the significance of G-protein coupled receptors (GPCRs) in connecting immune and epithelial cells, leading to novel therapies for EoE and IBD.
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Affiliation(s)
- Hassan Melhem
- Gastroenterology Group, Department of Biomedicine, University of Basel, 4031 Basel, Switzerland
| | - Jan Hendrik Niess
- Gastroenterology Group, Department of Biomedicine, University of Basel, 4031 Basel, Switzerland
- Department of Gastroenterology and Hepatology, University Digestive Healthcare Center, Clarunis, 4002 Basel, Switzerland
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13
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Zha P, Liu W, Zhou Y, Chen Y. Protective effects of chlorogenic acid on the intestinal barrier of broiler chickens: an immunological stress model study. Poult Sci 2024; 103:103949. [PMID: 38917604 PMCID: PMC11251075 DOI: 10.1016/j.psj.2024.103949] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2024] [Revised: 06/01/2024] [Accepted: 06/03/2024] [Indexed: 06/27/2024] Open
Abstract
This study was conducted to investigate the protective effects of chlorogenic acid (CGA) on inflammatory responses and intestinal health of lipopolysaccharide (LPS)-challenged broilers. One hundred and forty-four 1-day-old male broiler chicks were divided into 3 groups with 6 replicates of 8 birds each. The groups were as follows: 1) Control group: birds fed a basal diet; 2) LPS group: LPS-challenged birds fed a basal diet; 3) CGA group: LPS-challenged birds fed a CGA-supplemented diet. The LPS was intraperitoneally administered at a dose of 1 mg/kg of body weight. CGA increased the weight gain and feed intake of LPS-challenged birds by 37.05% and 24.29%, respectively (P < 0.05). CGA also alleviated LPS-induced inflammation, as evidenced by lower levels of pro-inflammatory cytokines in the serum and jejunum (tumor necrosis factor-α, interferon-γ, interleukin-1β, and interleukin-6), and the decreased myeloperoxidase activity in the jejunum (P < 0.05). These effects were accompanied by a decrease in the mRNA abundance of toll-like receptor 4 and myeloid differentiation factor 88 and an inhibition of nuclear factor kappa-B translocation in the jejunum (P < 0.05). CGA reduced circulating diamine oxidase activity and levels of D-lactate and endotoxin, and positively regulated the expression of jejunal claudin-3 and zonula occludens-1 in LPS-challenged broilers (P < 0.05). Compared to the LPS group, CGA reduced the apoptotic rate of epithelial cells and cytochrome c concentration in the jejunum, and normalized the expression of genes responsible for proliferation and apoptosis in jejunal epithelial cells, including cysteine aspartate-specific protease-9, B cell lymphoma-2, and proliferating cell nuclear antigen (P < 0.05). Furthermore, CGA normalized the altered phosphorylation of protein kinase B and glycogen synthase kinase-3β, as well as the translocation of nuclear β-catenin in the jejunum of LPS-challenged broilers (P < 0.05). These results suggested that CGA supplementation improved growth performance, alleviated inflammation, and helped maintain intestinal integrity and barrier function in LPS-challenged broilers, possibly through the regulation of the toll-like receptor 4/nuclear factor kappa-B and protein kinase B/Wnt/β-catenin pathways.
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Affiliation(s)
- Pingping Zha
- College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, People's Republic of China
| | - Wenhan Liu
- College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, People's Republic of China
| | - Yanmin Zhou
- College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, People's Republic of China
| | - Yueping Chen
- College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, People's Republic of China.
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14
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Rupar MJ, Hanson H, Rogers S, Botlick B, Trimmer S, Hickman JJ. Modelling the innate immune system in microphysiological systems. LAB ON A CHIP 2024; 24:3604-3625. [PMID: 38957150 PMCID: PMC11264333 DOI: 10.1039/d3lc00812f] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/25/2023] [Accepted: 05/09/2024] [Indexed: 07/04/2024]
Abstract
This critical review aims to highlight how modeling of the immune response has adapted over time to utilize microphysiological systems. Topics covered here will discuss the integral components of the immune system in various human body systems, and how these interactions are modeled using these systems. Through the use of microphysiological systems, we have not only expanded on foundations of basic immune cell information, but have also gleaned insight on how immune cells work both independently and collaboratively within an entire human body system.
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Affiliation(s)
- Michael J Rupar
- Hesperos, Inc., 12501 Research Parkway, Suite 100, Orlando, FL 32826, USA.
| | - Hannah Hanson
- Hesperos, Inc., 12501 Research Parkway, Suite 100, Orlando, FL 32826, USA.
| | - Stephanie Rogers
- Hesperos, Inc., 12501 Research Parkway, Suite 100, Orlando, FL 32826, USA.
| | - Brianna Botlick
- Hesperos, Inc., 12501 Research Parkway, Suite 100, Orlando, FL 32826, USA.
| | - Steven Trimmer
- Hesperos, Inc., 12501 Research Parkway, Suite 100, Orlando, FL 32826, USA.
| | - James J Hickman
- Hesperos, Inc., 12501 Research Parkway, Suite 100, Orlando, FL 32826, USA.
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15
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Li J, Li J, Liu Y, Zeng J, Liu Y, Wu Y. Large-scale bidirectional Mendelian randomization study identifies new gut microbiome significantly associated with immune thrombocytopenic purpura. Front Microbiol 2024; 15:1423951. [PMID: 39027091 PMCID: PMC11257036 DOI: 10.3389/fmicb.2024.1423951] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2024] [Accepted: 06/18/2024] [Indexed: 07/20/2024] Open
Abstract
Introduction A variety of studies have shown a link between the gut microbiota and autoimmune diseases, but the causal relationship with Henoch-Schönlein purpura (HSP) and immune thrombocytopenic purpura (ITP) is unknown. Methods This study investigated the bidirectional causality between gut microbiota and HSP and ITP using Mendelian randomization (MR). Large-scale genetic data of gut microbiota at phylum to species level from the MiBioGen consortium and the Dutch Microbiome Project were utilized. Genome-wide association studies (GWAS) summary statistics for HSP and ITP came from FinnGen R10. Various MR methods were applied to infer causal relationships, including inverse variance weighted (IVW), maximum likelihood (ML), cML-MA, MR-Egger, weighted median, weighted model, and MR-PRESSO. Multiple sensitivity analyses and Bonferroni correction were conducted to enhance robustness and reliability. Results Based on the IVW estimates, 23 bacterial taxa were identified to have suggestive associations with HSP and ITP. Remarkably, after Bonferroni correction, family Alcaligenaceae (OR = 2.86, 95% CI = 1.52-5.37; IVW, p = 1.10 × 10-3, ML, p = 1.40 × 10-3) was significantly associated with ITP as a risk factor, while family Bacteroidales S24 7group (OR = 0.46, 95% CI = 0.29-0.74; IVW, p = 1.40 × 10-3) was significantly associated with ITP as a protective factor. No significant associations between HSP and ITP and gut microbiota were found in reverse analyses. Conclusion Our study provides evidence of causal effects of gut microbiota on HSP and ITP, highlighting the importance of further research to clarify the underlying mechanisms and develop targeted therapeutic interventions for these autoimmune diseases.
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Affiliation(s)
- Jiawei Li
- School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Jia Li
- School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yuxiao Liu
- School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Juanhuan Zeng
- School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yuan Liu
- School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yeke Wu
- Department of Stomatology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
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Li J, Wei Z, Lou F, Zhang X, Duan J, Luo C, Hu X, Tu P, Liu L, Zhong R, Chen L, Du X, Zhang H. Disrupted Microbiota of Colon Results in Worse Immunity and Metabolism in Low-Birth-Weight Jinhua Newborn Piglets. Microorganisms 2024; 12:1371. [PMID: 39065139 PMCID: PMC11278573 DOI: 10.3390/microorganisms12071371] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2024] [Revised: 05/31/2024] [Accepted: 06/04/2024] [Indexed: 07/28/2024] Open
Abstract
The Jinhua pig is well known in China due to its delicious meat. However, because of large litter size, low birth weight always happens. This experiment used this breed as a model to research bacterial evidence leading to growth restriction and provide a possible solution linked to probiotics. In this experiment, the differences in organs indexes, colonic morphology, short chain fatty acid (SCFA) concentrations, microbiome, and transcriptome were detected between piglets in the standard-birth-weight group (SG) and low-birth-weight group (LG) to find potential evidence leading to low birth weight. We found that LG piglets had a lower liver index (p < 0.05), deeper colonic crypt depth (p < 0.05), fewer goblet cells (p < 0.05), and more inflammatory factor infiltration. In addition, differentially expressed genes (DEGs) were mainly enriched in B-cell immunity and glucose metabolism, and LG piglets had lower concentrations of SCFAs, especially butyrate and isobutyrate (p < 0.05). Finally, most of the significantly differentially abundant microbes were fewer in LG piglets, which affected DEG expressions and SCFA concentrations further resulting in worse energy metabolism and immunity. In conclusion, colonic disrupted microbiota may cause worse glucose metabolism, immunity, and SCFA production in LG piglets, and beneficial microbes colonized in SG piglets may benefit these harmful changes.
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Affiliation(s)
- Jiaheng Li
- Institute of Animal Husbandry and Veterinary Medicine, Jinhua Academy of Agricultural Sciences, Jinhua 321011, China; (J.L.); (F.L.); (X.Z.); (X.H.); (P.T.); (X.D.)
- State Key Laboratory of Animal Nutrition and Feeding, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China; (Z.W.); (J.D.); (C.L.); (L.L.); (L.C.); (H.Z.)
- Precision Livestock and Nutrition Unit, Gembloux Agro-Bio Tech, TERRA Teaching and Research Centre, Liège University, Passage des Déportés 2, 5030 Gembloux, Belgium
| | - Zeou Wei
- State Key Laboratory of Animal Nutrition and Feeding, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China; (Z.W.); (J.D.); (C.L.); (L.L.); (L.C.); (H.Z.)
- School of Agriculture and Food Science, University College Dublin, Belfeld, D04 V1W8 Dublin, Ireland
| | - Fangfang Lou
- Institute of Animal Husbandry and Veterinary Medicine, Jinhua Academy of Agricultural Sciences, Jinhua 321011, China; (J.L.); (F.L.); (X.Z.); (X.H.); (P.T.); (X.D.)
| | - Xiaojun Zhang
- Institute of Animal Husbandry and Veterinary Medicine, Jinhua Academy of Agricultural Sciences, Jinhua 321011, China; (J.L.); (F.L.); (X.Z.); (X.H.); (P.T.); (X.D.)
| | - Jiujun Duan
- State Key Laboratory of Animal Nutrition and Feeding, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China; (Z.W.); (J.D.); (C.L.); (L.L.); (L.C.); (H.Z.)
| | - Chengzeng Luo
- State Key Laboratory of Animal Nutrition and Feeding, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China; (Z.W.); (J.D.); (C.L.); (L.L.); (L.C.); (H.Z.)
| | - Xujin Hu
- Institute of Animal Husbandry and Veterinary Medicine, Jinhua Academy of Agricultural Sciences, Jinhua 321011, China; (J.L.); (F.L.); (X.Z.); (X.H.); (P.T.); (X.D.)
| | - Pingguang Tu
- Institute of Animal Husbandry and Veterinary Medicine, Jinhua Academy of Agricultural Sciences, Jinhua 321011, China; (J.L.); (F.L.); (X.Z.); (X.H.); (P.T.); (X.D.)
| | - Lei Liu
- State Key Laboratory of Animal Nutrition and Feeding, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China; (Z.W.); (J.D.); (C.L.); (L.L.); (L.C.); (H.Z.)
| | - Ruqing Zhong
- State Key Laboratory of Animal Nutrition and Feeding, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China; (Z.W.); (J.D.); (C.L.); (L.L.); (L.C.); (H.Z.)
| | - Liang Chen
- State Key Laboratory of Animal Nutrition and Feeding, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China; (Z.W.); (J.D.); (C.L.); (L.L.); (L.C.); (H.Z.)
| | - Xizhong Du
- Institute of Animal Husbandry and Veterinary Medicine, Jinhua Academy of Agricultural Sciences, Jinhua 321011, China; (J.L.); (F.L.); (X.Z.); (X.H.); (P.T.); (X.D.)
| | - Hongfu Zhang
- State Key Laboratory of Animal Nutrition and Feeding, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China; (Z.W.); (J.D.); (C.L.); (L.L.); (L.C.); (H.Z.)
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Yang CT, Yen HH, Su PY, Chen YY, Huang SP. High prevalence of vitamin D deficiency in Taiwanese patients with inflammatory bowel disease. Sci Rep 2024; 14:14091. [PMID: 38890510 PMCID: PMC11189481 DOI: 10.1038/s41598-024-64930-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2024] [Accepted: 06/14/2024] [Indexed: 06/20/2024] Open
Abstract
Vitamin D deficiency is common in patients with inflammatory bowel disease (IBD). In this study, we aimed to evaluate the prevalence and risk factors of vitamin D deficiency in a Taiwanese IBD cohort. Vitamin D levels were checked in adult patients with IBD who were treated at Changhua Christian Hospital, a medical center in central Taiwan, from January 2017 to December 2023. The risk factors for vitamin D deficiency were evaluated. 106 adult IBD patients were included, including 20 patients with Crohn's disease and 86 with ulcerative colitis. The median age at diagnosis was 39.2 years. The mean vitamin D level was 22.2 ± 8 ng/mL. Forty-five patients (42.5%) had vitamin D deficiency (vitamin D level < 20 ng/mL). Comparing patients with normal vitamin D levels and those with vitamin D deficiency after multivariate adjustment, female sex and early age at diagnosis were identified as statistically significant risk factors. We found a prevalence of 42.5% of vitamin D deficiency in the Taiwanese IBD population. Understanding this issue is essential for teaching patients and doctors about vitamin D deficiency screening and improving patient outcomes.
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Affiliation(s)
- Chen-Ta Yang
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, 400, Taiwan
- Division of Gastroenterology, Changhua Christian Hospital, Changhua, 500, Taiwan
| | - Hsu-Heng Yen
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, 400, Taiwan.
- Division of Gastroenterology, Changhua Christian Hospital, Changhua, 500, Taiwan.
| | - Pei-Yuan Su
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, 400, Taiwan
- Division of Gastroenterology, Changhua Christian Hospital, Changhua, 500, Taiwan
| | - Yang-Yuan Chen
- Division of Gastroenterology, Changhua Christian Hospital, Changhua, 500, Taiwan
- Department of Hospitality Management, MingDao University, Changhua, 500, Taiwan
| | - Siou-Ping Huang
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, 400, Taiwan
- Division of Gastroenterology, Changhua Christian Hospital, Changhua, 500, Taiwan
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18
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Kaushik G, Vashishtha R, Verma C, Sharma S, Kumar V. Genetic Variation in Toll-Like Receptors (TLRs) 2, 4, and 9 Influences HIV Disease Progression Toward Active TB and AIDS. J Inflamm Res 2024; 17:3283-3291. [PMID: 38800599 PMCID: PMC11128240 DOI: 10.2147/jir.s451431] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2023] [Accepted: 03/25/2024] [Indexed: 05/29/2024] Open
Abstract
Background Toll-like receptors (TLRs) are identified as one of the key components of the innate immune system. The objective of this study was to explore the influence of genetic variability in these TLRs on human immunodeficiency virus (HIV) disease progression with and without tuberculosis (TB) co-infection. Materials and Methods This prospective, cross-sectional, and longitudinal study included 373 HIV-positive patients without TB infection. This study aimed to examine the genetic variation in TLRs (TLR2, TLR4, and TLR9) between patients with HIV-1 infection and those who progressed to active TB during the two years of follow-up. Results During the two year follow-up of 373 positive patients, 98 patients progressed to active TB/AIDS (acquired immunodeficiency syndrome). When comparing 98 HIV patients who developed active TB/AIDS to 275 HIV patients who did not, it was discovered that the frequency of the A allele in TLR9 was considerably higher (p <0.001) in HIV patients progressed to active TB/AIDS. Ninety eight HIV individuals who advanced to active TB/AIDS showed a significantly higher frequency of the AA genotype in TLR9 than did in HIV patients who had no TB/AIDS (p <0.001). Conclusion The increased association of the AA genotype of TLR9 in HIV patients who progressed to active TB during follow-up suggests that HIV-positive patients with the AA genotype of TLR9 have increased susceptibility towards TB during the disease progression.
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Affiliation(s)
- Gaurav Kaushik
- School of Allied Health Sciences, Sharda University, Greater Noida, Uttar Pradesh, 201310, India
- Department of Medicine, All India Institute of Medical Sciences, New Delhi, 110029, India
| | - Richa Vashishtha
- Department of Medicine, All India Institute of Medical Sciences, New Delhi, 110029, India
| | - Chaitenya Verma
- Department of Pathology, Wexner Medical Center, Ohio State University, Columbus, OH, USA
| | - Shipra Sharma
- Shri Guru Ram Rai Institute of Medical & Health Sciences, Dehradun, Uttarakhand, 248001, India
| | - Vinay Kumar
- Pennsylvania State University Hershey Medical Center, 500 University Dr, Hershey, PA, 17033, USA
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19
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Hu X, Yuan X, Zhang G, Song H, Ji P, Guo Y, Liu Z, Tian Y, Shen R, Wang D. The intestinal epithelial-macrophage-crypt stem cell axis plays a crucial role in regulating and maintaining intestinal homeostasis. Life Sci 2024; 344:122452. [PMID: 38462226 DOI: 10.1016/j.lfs.2024.122452] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2023] [Revised: 01/18/2024] [Accepted: 01/18/2024] [Indexed: 03/12/2024]
Abstract
The intestinal tract plays a vital role in both digestion and immunity, making its equilibrium crucial for overall health. This equilibrium relies on the dynamic interplay among intestinal epithelial cells, macrophages, and crypt stem cells. Intestinal epithelial cells play a pivotal role in protecting and regulating the gut. They form vital barriers, modulate immune responses, and engage in pathogen defense and cytokine secretion. Moreover, they supervise the regulation of intestinal stem cells. Macrophages, serving as immune cells, actively influence the immune response through the phagocytosis of pathogens and the release of cytokines. They also contribute to regulating intestinal stem cells. Stem cells, known for their self-renewal and differentiation abilities, play a vital role in repairing damaged intestinal epithelium and maintaining homeostasis. Although research has primarily concentrated on the connections between epithelial and stem cells, interactions with macrophages have been less explored. This review aims to fill this gap by exploring the roles of the intestinal epithelial-macrophage-crypt stem cell axis in maintaining intestinal balance. It seeks to unravel the intricate dynamics and regulatory mechanisms among these essential players. A comprehensive understanding of these cell types' functions and interactions promises insights into intestinal homeostasis regulation. Moreover, it holds potential for innovative approaches to manage conditions like radiation-induced intestinal injury, inflammatory bowel disease, and related diseases.
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Affiliation(s)
- Xiaohui Hu
- School of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu Province 73000, China.
| | - Xinyi Yuan
- School of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu Province 73000, China.
| | - Guokun Zhang
- School of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu Province 73000, China.
| | - Haoyun Song
- School of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu Province 73000, China.
| | - Pengfei Ji
- School of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu Province 73000, China.
| | - Yanan Guo
- School of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu Province 73000, China.
| | - Zihua Liu
- Lanzhou University Second Hospital, Lanzhou University, Lanzhou, Gansu Province 73000, China
| | - Yixiao Tian
- School of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu Province 73000, China.
| | - Rong Shen
- School of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu Province 73000, China.
| | - Degui Wang
- School of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu Province 73000, China; NHC Key Laboratory of Diagnosis and Therapy of Gastrointestinal Tumor, Lanzhou, Gansu Province 730000, China.
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20
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Cheung KL, Zhao L, Sharma R, Ghosh AA, Appiah M, Sun Y, Jaganathan A, Hu Y, LeJeune A, Xu F, Han X, Wang X, Zhang F, Ren C, Walsh MJ, Xiong H, Tsankov A, Zhou MM. Class IIa HDAC4 and HDAC7 cooperatively regulate gene transcription in Th17 cell differentiation. Proc Natl Acad Sci U S A 2024; 121:e2312111121. [PMID: 38657041 PMCID: PMC11067014 DOI: 10.1073/pnas.2312111121] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2023] [Accepted: 03/21/2024] [Indexed: 04/26/2024] Open
Abstract
Class II histone deacetylases (HDACs) are important in regulation of gene transcription during T cell development. However, our understanding of their cell-specific functions is limited. In this study, we reveal that class IIa Hdac4 and Hdac7 (Hdac4/7) are selectively induced in transcription, guiding the lineage-specific differentiation of mouse T-helper 17 (Th17) cells from naive CD4+ T cells. Importantly, Hdac4/7 are functionally dispensable in other Th subtypes. Mechanistically, Hdac4 interacts with the transcription factor (TF) JunB, facilitating the transcriptional activation of Th17 signature genes such as Il17a/f. Conversely, Hdac7 collaborates with the TF Aiolos and Smrt/Ncor1-Hdac3 corepressors to repress transcription of Th17 negative regulators, including Il2, in Th17 cell differentiation. Inhibiting Hdac4/7 through pharmacological or genetic methods effectively mitigates Th17 cell-mediated intestinal inflammation in a colitis mouse model. Our study uncovers molecular mechanisms where HDAC4 and HDAC7 function distinctively yet cooperatively in regulating ordered gene transcription during Th17 cell differentiation. These findings suggest a potential therapeutic strategy of targeting HDAC4/7 for treating Th17-related inflammatory diseases, such as ulcerative colitis.
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Affiliation(s)
- Ka Lung Cheung
- Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY10029
| | - Li Zhao
- Institute of Epigenetic Medicine of the First Hospital, Jilin University, Changchun130061, China
| | - Rajal Sharma
- Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY10029
| | - Anurupa Abhijit Ghosh
- Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY10029
| | - Michael Appiah
- Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY10029
| | - Yifei Sun
- Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY10029
| | - Anbalagan Jaganathan
- Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY10029
| | - Yuan Hu
- Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY10029
| | - Alannah LeJeune
- Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY10029
| | - Feihong Xu
- Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY10029
| | - Xinye Han
- Institute of Epigenetic Medicine of the First Hospital, Jilin University, Changchun130061, China
| | - Xueting Wang
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY10029
| | - Fan Zhang
- Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY10029
| | - Chunyan Ren
- Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY10029
| | - Martin J. Walsh
- Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY10029
| | - Huabao Xiong
- Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY10029
| | - Alexander Tsankov
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY10029
| | - Ming-Ming Zhou
- Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY10029
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21
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Ouyang Q, Li X, Liang Y, Liu R. Sea Buckthorn Polysaccharide Ameliorates Colitis. Nutrients 2024; 16:1280. [PMID: 38732527 PMCID: PMC11085905 DOI: 10.3390/nu16091280] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2023] [Revised: 11/07/2023] [Accepted: 11/09/2023] [Indexed: 05/13/2024] Open
Abstract
Ulcerative colitis (UC) is characterized by chronic inflammation and ulceration of the intestinal inner lining, resulting in various symptoms. Sea buckthorn berries contain a bioactive compound known as sea buckthorn polysaccharide (SBP). However, the precise mechanisms underlying the impact of SBP on UC remain unclear. In this study, we investigated the effects of pretreatment with SBP on colitis induced by DSS. Our findings demonstrate that SBP pretreatment effectively reduces inflammation, oxidative stress, and intestinal barrier damage associated with colitis. To further elucidate the role of SBP-modulated gut microbiota in UC, we performed fecal microbiota transplantation (FMT) on DSS-treated mice. The microbiota from SBP-treated mice exhibits notable anti-inflammatory and antioxidant effects, improves colonic barrier integrity, and increases the abundance of beneficial bacteria, as well as enhancing SCFA production. Collectively, these results strongly indicate that SBP-mediated amelioration of colitis is attributed to its impact on the gut microbiota, particularly through the promotion of SCFA-producing bacteria and subsequent elevation of SCFA levels. This study provides compelling evidence supporting the efficacy of pre-emptive SBP supplementation in alleviating colitis symptoms by modulating the gut microbiota, thereby offering novel insights into the potential of SBP as a regulator of the gut microbiota for colitis relief.
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Affiliation(s)
- Qinqin Ouyang
- College of Life Sciences, Nanjing Agricultural University, Nanjing 210000, China; (Q.O.)
| | - Xin Li
- College of Food Science and Technology, Nanjing Agricultural University, Nanjing 210000, China
| | - Yongheng Liang
- College of Life Sciences, Nanjing Agricultural University, Nanjing 210000, China; (Q.O.)
| | - Rong Liu
- College of Food Science and Technology, Nanjing Agricultural University, Nanjing 210000, China
- Department of Nutrition and Health, China Agricultural University, Beijing 100083, China
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22
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Ali A, Wu L, Ali SS. Gut microbiota and acute kidney injury: immunological crosstalk link. Int Urol Nephrol 2024; 56:1345-1358. [PMID: 37749436 DOI: 10.1007/s11255-023-03760-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2023] [Accepted: 08/14/2023] [Indexed: 09/27/2023]
Abstract
The gut microbiota, often called the "forgotten organ," plays a crucial role in bidirectional communication with the host for optimal physiological function. This communication helps regulate the host's immunity and metabolism positively and negatively. Many factors influence microbiota homeostasis and subsequently lead to an immune system imbalance. The correlation between an unbalanced immune system and acute diseases such as acute kidney injury is not fully understood, and the role of gut microbiota in disease pathogenesis is still yet uncovered. This review summarizes our understanding of gut microbiota, focusing on the interactions between the host's immune system and the microbiome and their impact on acute kidney injury.
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Affiliation(s)
- Asmaa Ali
- Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, 212013, China.
- Department of Pulmonary Medicine, Abbassia Chest Hospital, MOH, Cairo, Egypt.
- Department of Respiratory Allergy, A Al-Rashed Allergy Center, Ministry of Health, Kuwait, Kuwait.
| | - Liang Wu
- Yizheng Hospital, Nanjing Drum Tower Hospital Group, Yizheng, 210008, China.
| | - Sameh Samir Ali
- School of the Environment and Safety Engineering, Biofuels Institute, Jiangsu University, Zhenjiang, 212013, China
- Botany Department, Faculty of Science, Tanta University, Tanta, 31527, Egypt
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23
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Cao R, Fang X, Li Z, Li S, Guo Q, Chai Y. Effect of Polygonatum sibiricum saponins on gut microbiota of mice with ulcerative colitis. Fitoterapia 2024; 174:105855. [PMID: 38354822 DOI: 10.1016/j.fitote.2024.105855] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2023] [Revised: 02/05/2024] [Accepted: 02/11/2024] [Indexed: 02/16/2024]
Abstract
Polygonatum sibiricum is a plant with medicinal and nutritional properties. Saponins are the important biologically active components of Polygonatum sibiricum. In this study, the specific components of Polygonatum sibiricum saponins (PSS) were analyzed, and the regulation effect of PSS on intestinal flora in patients with ulcerative colitis (UC) was investigated by inducing male Kunming mice with dextran sulfate sodium (DSS). PSS could ameliorate the symptoms of weight loss, high DAI score and colon length reduction compared to DSS-induced treatment. Colonic fragments were taken for H&E staining and histopathological scoring. PSS could significantly improve the pathological abnormality of colitis mice. 16S rRNA analysis showed that the intestinal microbial community of mice treated with DSS was significantly damaged. PSS could restore the richness and diversity of intestinal microbial flora, reduce the number of pathogenic bacteria, and increase the abundance of Lactobacillus spp. and Muribaculaceae, and improve the intestinal microbial flora disorder. Generally, PSS had an obvious effect in relieving colitis in mice. This study confirmed that Polygonatum sibiricum saponins play a therapeutic and palliative role in ulcerative colitis by regulating the microbiome balance.
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Affiliation(s)
- Rong Cao
- College of Life Sciences, Northeast Forestry University, Harbin 150040, China
| | - Xinyi Fang
- College of Life Sciences, Northeast Forestry University, Harbin 150040, China
| | - Ziyi Li
- College of Life Sciences, Northeast Forestry University, Harbin 150040, China
| | - Sijia Li
- College of Life Sciences, Northeast Forestry University, Harbin 150040, China
| | - Qingqi Guo
- College of Life Sciences, Northeast Forestry University, Harbin 150040, China; Key Laboratory of Forest Food Resources Utilization of Heilongjiang Province, Harbin 150040, China
| | - Yangyang Chai
- College of Life Sciences, Northeast Forestry University, Harbin 150040, China; Key Laboratory of Forest Food Resources Utilization of Heilongjiang Province, Harbin 150040, China.
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24
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Plaza J, Mínguez A, Bastida G, Marqués R, Nos P, Poveda JL, Moret-Tatay I. Genetic Variants Associated with Biological Treatment Response in Inflammatory Bowel Disease: A Systematic Review. Int J Mol Sci 2024; 25:3717. [PMID: 38612528 PMCID: PMC11012229 DOI: 10.3390/ijms25073717] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2024] [Revised: 03/05/2024] [Accepted: 03/21/2024] [Indexed: 04/14/2024] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the digestive tract usually characterized by diarrhea, rectal bleeding, and abdominal pain. IBD includes Crohn's disease and ulcerative colitis as the main entities. IBD is a debilitating condition that can lead to life-threatening complications, involving possible malignancy and surgery. The available therapies aim to achieve long-term remission and prevent disease progression. Biologics are bioengineered therapeutic drugs that mainly target proteins. Although they have revolutionized the treatment of IBD, their potential therapeutic benefits are limited due to large interindividual variability in clinical response in terms of efficacy and toxicity, resulting in high rates of long-term therapeutic failure. It is therefore important to find biomarkers that provide tailor-made treatment strategies that allow for patient stratification to maximize treatment benefits and minimize adverse events. Pharmacogenetics has the potential to optimize biologics selection in IBD by identifying genetic variants, specifically single nucleotide polymorphisms (SNPs), which are the underlying factors associated with an individual's drug response. This review analyzes the current knowledge of genetic variants associated with biological agent response (infliximab, adalimumab, ustekinumab, and vedolizumab) in IBD. An online literature search in various databases was conducted. After applying the inclusion and exclusion criteria, 28 reports from the 1685 results were employed for the review. The most significant SNPs potentially useful as predictive biomarkers of treatment response are linked to immunity, cytokine production, and immunorecognition.
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Affiliation(s)
- Javier Plaza
- Inflammatory Bowel Disease Research Group, Health Research Institute La Fe (IIS La Fe), 46026 Valencia, Spain; (J.P.); (A.M.)
- Department of Pharmacy and Pharmaceutical Technology and Parasitology, University of Valencia, 46100 Valencia, Spain
| | - Alejandro Mínguez
- Inflammatory Bowel Disease Research Group, Health Research Institute La Fe (IIS La Fe), 46026 Valencia, Spain; (J.P.); (A.M.)
- Inflammatory Bowel Disease Unit, Gastroenterology Department, La Fe University and Polytechnic Hospital, 46026 Valencia, Spain; (G.B.); (P.N.)
| | - Guillermo Bastida
- Inflammatory Bowel Disease Unit, Gastroenterology Department, La Fe University and Polytechnic Hospital, 46026 Valencia, Spain; (G.B.); (P.N.)
| | - Remedios Marqués
- Pharmacy Department, La Fe University and Polytechnic Hospital, 46026 Valencia, Spain; (R.M.); (J.L.P.)
| | - Pilar Nos
- Inflammatory Bowel Disease Unit, Gastroenterology Department, La Fe University and Polytechnic Hospital, 46026 Valencia, Spain; (G.B.); (P.N.)
| | - Jose Luis Poveda
- Pharmacy Department, La Fe University and Polytechnic Hospital, 46026 Valencia, Spain; (R.M.); (J.L.P.)
| | - Inés Moret-Tatay
- Inflammatory Bowel Disease Research Group, Health Research Institute La Fe (IIS La Fe), 46026 Valencia, Spain; (J.P.); (A.M.)
- General Directorate of Public Health, Council of Healthcare, 46021 Valencia, Spain
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25
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Torres-Huerta A, Ruley-Haase K, Reed T, Boger-May A, Rubadeux D, Mayer L, Rajashekara AM, Hiller M, Frech M, Roncagli C, Pedersen C, Camacho MC, Hollmer L, English L, Kane G, Boone DL. Retinoid orphan receptor gamma t (rorγt) promotes inflammatory eosinophilia but is dispensable for innate immune-mediated colitis. PLoS One 2024; 19:e0300892. [PMID: 38512959 PMCID: PMC10956760 DOI: 10.1371/journal.pone.0300892] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2023] [Accepted: 03/05/2024] [Indexed: 03/23/2024] Open
Abstract
Inflammatory bowel diseases (IBD) result from uncontrolled inflammation in the intestinal mucosa leading to damage and loss of function. Both innate and adaptive immunity contribute to the inflammation of IBD and innate and adaptive immune cells reciprocally activate each other in a forward feedback loop. In order to better understand innate immune contributions to IBD, we developed a model of spontaneous 100% penetrant, early onset colitis that occurs in the absence of adaptive immunity by crossing villin-TNFAIP3 mice to RAG1-/- mice (TRAG mice). This model is driven by microbes and features increased levels of innate lymphoid cells in the intestinal mucosa. To investigate the role of type 3 innate lymphoid cells (ILC3) in the innate colitis of TRAG mice, we crossed them to retinoid orphan receptor gamma t deficient (Rorγt-/-) mice. Rorγt-/- x TRAG mice exhibited markedly reduced eosinophilia in the colonic mucosa, but colitis persisted in these mice. Colitis in Rorγt-/- x TRAG mice was characterized by increased infiltration of the intestinal mucosa by neutrophils, inflammatory monocytes, macrophages and other innate cells. RNA and cellular profiles of Rorγt-/- x TRAG mice were consistent with a lack of ILC3 and ILC3 derived cytokines, reduced antimicrobial factors, increased activation oof epithelial repair processes and reduced activation of epithelial cell STAT3. The colitis in Rorγt-/- x TRAG mice was ameliorated by antibiotic treatment indicating that microbes contribute to the ILC3-independent colitis of these mice. Together, these gene expression and cell signaling signatures reflect the double-edged sword of ILC3 in the intestine, inducing both proinflammatory and antimicrobial protective responses. Thus, Rorγt promotes eosinophilia but Rorγt and Rorγt-dependent ILC3 are dispensable for the innate colitis in TRAG mice.
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Affiliation(s)
- Alvaro Torres-Huerta
- Department of Microbiology & Immunology, Indiana University School of Medicine-South Bend, South Bend, IN, United States of America
| | - Katelyn Ruley-Haase
- Department of Biology, University of Notre Dame, South Bend, IN, United States of America
| | - Theodore Reed
- Department of Biology, University of Notre Dame, South Bend, IN, United States of America
| | - Antonia Boger-May
- Department of Microbiology & Immunology, Indiana University School of Medicine-South Bend, South Bend, IN, United States of America
| | - Derek Rubadeux
- Department of Biology, University of Notre Dame, South Bend, IN, United States of America
| | - Lauren Mayer
- Department of Biology, University of Notre Dame, South Bend, IN, United States of America
| | | | - Morgan Hiller
- Department of Biology, University of Notre Dame, South Bend, IN, United States of America
| | - Madeleine Frech
- Department of Biology, University of Notre Dame, South Bend, IN, United States of America
| | - Connor Roncagli
- Department of Biology, University of Notre Dame, South Bend, IN, United States of America
| | - Cameron Pedersen
- Department of Biology, University of Notre Dame, South Bend, IN, United States of America
| | - Mary Catherine Camacho
- Department of Biology, University of Notre Dame, South Bend, IN, United States of America
| | - Lauren Hollmer
- Department of Biology, University of Notre Dame, South Bend, IN, United States of America
| | - Lauren English
- Department of Biology, University of Notre Dame, South Bend, IN, United States of America
| | - Grace Kane
- Department of Biology, University of Notre Dame, South Bend, IN, United States of America
| | - David L. Boone
- Department of Microbiology & Immunology, Indiana University School of Medicine-South Bend, South Bend, IN, United States of America
- Department of Biology, University of Notre Dame, South Bend, IN, United States of America
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26
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Ou Y, Yang Z, Zhou Y, Yue H, Hua L, Liu Z, Lin G, Cai H, Chen Y, Hu W, Sun P. Antagonizing interleukin-5 receptor ameliorates dextran sulfate sodium-induced experimental colitis in mice through reducing NLRP3 inflammasome activation. Eur J Pharmacol 2024; 965:176331. [PMID: 38220140 DOI: 10.1016/j.ejphar.2024.176331] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2023] [Revised: 01/03/2024] [Accepted: 01/12/2024] [Indexed: 01/16/2024]
Abstract
Inflammatory bowel disease (IBD) is a condition characterized by inflammation in the gastrointestinal tract. Reducing intestinal inflammation is a promising approach for treating IBD. The nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome, a critical component of the innate immune system, is implicated in the pathogenesis of IBD. Therefore, inhibiting NLRP3 inflammasome activation is a potential therapeutic strategy for IBD. In this study, we investigated the effects of the interleukin-5 (IL-5) receptor antagonist YM-90709 on dextran sulfate sodium-induced experimental colitis in mice. We found that YM-90709 reduced the expressions of IL-1β and caspase-1 p20 in the colon and ameliorated colitis. Furthermore, we identified YM-90709 as an effective agent for inhibiting NLRP3 inflammasome activation. Knockdown of IL-5 receptor or using an inhibitor of STAT5, a key transcription factor downstream of the IL-5/IL-5 receptor signal pathway, also reduced NLRP3 inflammasome-dependent IL-1β release and ASC speck formation. Our study is the first to demonstrate that the NLRP3 inflammasome may be a downstream signal of IL-5/IL-5 receptor and that YM-90709 protects against IBD by inhibiting IL-5 receptor. These findings suggest a new strategy for regulating intestinal inflammation and managing IBD.
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Affiliation(s)
- Yitao Ou
- The Fifth Affiliated Hospital, Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, The NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, 511436, China
| | - Zhongjin Yang
- The Fifth Affiliated Hospital, Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, The NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, 511436, China
| | - Yinghua Zhou
- The Fifth Affiliated Hospital, Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, The NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, 511436, China
| | - Hu Yue
- The Fifth Affiliated Hospital, Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, The NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, 511436, China
| | - Lei Hua
- The Fifth Affiliated Hospital, Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, The NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, 511436, China
| | - Zhuorong Liu
- The Fifth Affiliated Hospital, Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, The NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, 511436, China
| | - Geng Lin
- The Fifth Affiliated Hospital, Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, The NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, 511436, China
| | - Haowei Cai
- The Fifth Affiliated Hospital, Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, The NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, 511436, China
| | - Yanhong Chen
- The Fifth Affiliated Hospital, Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, The NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, 511436, China
| | - Wenhui Hu
- The Fifth Affiliated Hospital, Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, The NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, 511436, China.
| | - Ping Sun
- The Fifth Affiliated Hospital, Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, The NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, 511436, China.
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Chen Z, Li J, Ma Q, Pikov V, Li M, Wang L, Liu Y, Ni M. Anti-Inflammatory Effects of Two-Week Sacral Nerve Stimulation Therapy in Patients With Ulcerative Colitis. Neuromodulation 2024; 27:360-371. [PMID: 37055336 DOI: 10.1016/j.neurom.2023.01.019] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2022] [Revised: 12/24/2022] [Accepted: 01/03/2023] [Indexed: 04/15/2023]
Abstract
BACKGROUND AND AIMS Sacral nerve stimulation (SNS) showed anti-inflammatory properties in animal models of inflammatory bowel disease. We aimed to evaluate the effectiveness and safety of SNS in patients with ulcerative colitis (UC). MATERIALS AND METHODS Twenty-six patients with mild and moderate disease were randomized into two groups: SNS (delivered at S3 and S4 sacral foramina) and sham-SNS (delivered 8-10 mm away from sacral foramina), with the therapy applied once daily for one hour, for two weeks. We evaluated the Mayo score and several exploratory biomarkers, including C-reactive protein in the plasma, pro-inflammatory cytokines and norepinephrine in the serum, assessment of autonomic activity, and diversity and abundance of fecal microbiota species. RESULTS After two weeks, 73% of the subjects in the SNS group achieved clinical response, compared with 27% in the sham-SNS group. Levels of C-reactive protein, pro-inflammatory cytokines in the serum, and autonomic activity were significantly improved toward a healthy profile in the SNS group but not in the sham-SNS group. Absolute abundance of fecal microbiota species and one of the metabolic pathways were changed in the SNS group but not in the sham-SNS group. Significant correlations were observed between pro-inflammatory cytokines and norepinephrine in the serum on the one side and fecal microbiota phyla on the other side. CONCLUSIONS Patients with mild and moderate UC were responsive to a two-week SNS therapy. After performing further studies to evaluate its efficacy and safety, temporary SNS delivered through acupuncture needles may become a useful screening tool for identifying SNS therapy responders before considering long-term implantation of the implantable pulse generator and SNS leads for performing long-term SNS therapy.
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Affiliation(s)
- Zhengxin Chen
- National Center for Colorectal Diseases, Nanjing Hospital of Traditional Chinese Medicine Affiliated to Nanjing University of Traditional Chinese Medicine, Nanjing, Jiangsu Province, China
| | - Jing Li
- Department of Acupuncture and Moxibustion, Nanjing Hospital of Traditional Chinese Medicine Affiliated to Nanjing University of Traditional Chinese Medicine, Nanjing, Jiangsu Province, China
| | - Qiyao Ma
- Graduate School, Nanjing University of Traditional Chinese Medicine, Nanjing, Jiangsu Province, China; Anorectal Surgery of Zhongda Hospital Southeast University, Nanjing, Jiangsu Province, China
| | | | - Min Li
- National Center for Colorectal Diseases, Nanjing Hospital of Traditional Chinese Medicine Affiliated to Nanjing University of Traditional Chinese Medicine, Nanjing, Jiangsu Province, China
| | - Ling Wang
- Graduate School, Nanjing University of Traditional Chinese Medicine, Nanjing, Jiangsu Province, China
| | - Ying Liu
- National Center for Colorectal Diseases, Nanjing Hospital of Traditional Chinese Medicine Affiliated to Nanjing University of Traditional Chinese Medicine, Nanjing, Jiangsu Province, China
| | - Min Ni
- National Center for Colorectal Diseases, Nanjing Hospital of Traditional Chinese Medicine Affiliated to Nanjing University of Traditional Chinese Medicine, Nanjing, Jiangsu Province, China.
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El Hadad J, Schreiner P, Vavricka SR, Greuter T. The Genetics of Inflammatory Bowel Disease. Mol Diagn Ther 2024; 28:27-35. [PMID: 37847439 PMCID: PMC10787003 DOI: 10.1007/s40291-023-00678-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/26/2023] [Indexed: 10/18/2023]
Abstract
The genetic background of inflammatory bowel disease, both Crohn's disease and ulcerative colitis, has been known for more than 2 decades. In the last 20 years, genome-wide association studies have dramatically increased our knowledge on the genetics of inflammatory bowel disease with more than 200 risk genes having been identified. Paralleling this increasing knowledge, the armamentarium of inflammatory bowel disease medications has been growing constantly. With more available therapeutic options, treatment decisions become more complex, with still many patients experiencing a debilitating disease course and a loss of response to treatment over time. With a better understanding of the disease, more effective personalized treatment strategies are looming on the horizon. Genotyping has long been considered a strategy for treatment decisions, such as the detection of thiopurine S-methyltransferase and nudix hydrolase 15 polymorphisms before the initiation of azathioprine. However, although many risk genes have been identified in inflammatory bowel disease, a substantial impact of genetic risk assessment on therapeutic strategies and disease outcome is still missing. In this review, we discuss the genetic background of inflammatory bowel disease, with a particular focus on the latest advances in the field and their potential impact on management decisions.
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Affiliation(s)
- Jasmina El Hadad
- Department of Internal Medicine, Triemli Hospital, Zurich, Switzerland
- Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | - Philipp Schreiner
- Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Stephan R Vavricka
- Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
- Center for Gastroenterology and Hepatology, Zurich, Switzerland
| | - Thomas Greuter
- Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland.
- Division of Gastroenterology and Hepatology, University Hospital Lausanne-CHUV, Lausanne, Switzerland.
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, GZO Zurich Regional Health Center, Spitalstrasse 66, 8620, Wetzikon, Switzerland.
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29
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Ragavan ML, Hemalatha S. The functional roles of short chain fatty acids as postbiotics in human gut: future perspectives. Food Sci Biotechnol 2024; 33:275-285. [PMID: 38222911 PMCID: PMC10786766 DOI: 10.1007/s10068-023-01414-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2023] [Revised: 07/26/2023] [Accepted: 08/07/2023] [Indexed: 01/16/2024] Open
Abstract
The significance of gut microbiome and their metabolites (postbiotics) on human health could be a promising approach to treat various diseases that includes inflammatory bowel diseases, colon cancer, and many neurological disorders. Probiotics with potential mental health benefits (psychobiotics) can alter the gut-brain axis via immunological, humoral, neuronal, and metabolic pathways. Recently, probiotic bacteria like Lactobacillus and Bifidobacterium have been demonstrated for SCFAs production, which play a crucial role in a variety of diseases. These acids could enhance the production of mucins, antimicrobial proteins (bacteriocins and peptides), cytokines (Interleukin 10 and 18) and neurotransmitters (serotonin) in the intestine to main the gut microbiota, intestinal barrier system and other immune functions. In this review, we discuss about two mechanisms such as (i) SCFAs mediated intestinal barrier system, and (ii) SCFAs mediated gut-brain axis to elucidate the therapeutic options for the treatment/prevention of various diseases.
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Affiliation(s)
| | - S. Hemalatha
- School of Life Sciences, BSACIST, Vandalur, Chennai, Tamil Nadu India
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Gambirasi M, Safa A, Vruzhaj I, Giacomin A, Sartor F, Toffoli G. Oral Administration of Cancer Vaccines: Challenges and Future Perspectives. Vaccines (Basel) 2023; 12:26. [PMID: 38250839 PMCID: PMC10821404 DOI: 10.3390/vaccines12010026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2023] [Revised: 12/19/2023] [Accepted: 12/22/2023] [Indexed: 01/23/2024] Open
Abstract
Cancer vaccines, a burgeoning strategy in cancer treatment, are exploring innovative administration routes to enhance patient and medical staff experiences, as well as immunological outcomes. Among these, oral administration has surfaced as a particularly noteworthy approach, which is attributed to its capacity to ignite both humoral and cellular immune responses at systemic and mucosal tiers, thereby potentially bolstering vaccine efficacy comprehensively and durably. Notwithstanding this, the deployment of vaccines through the oral route in a clinical context is impeded by multifaceted challenges, predominantly stemming from the intricacy of orchestrating effective oral immunogenicity and necessitating strategic navigation through gastrointestinal barriers. Based on the immunogenicity of the gastrointestinal tract, this review critically analyses the challenges and recent advances and provides insights into the future development of oral cancer vaccines.
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Affiliation(s)
- Marta Gambirasi
- Experimental and Clinical Pharmacology Unit, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS National Cancer Institute, 33081 Aviano, Italy; (M.G.); (I.V.); (F.S.)
- Department of Life Sciences, University of Trieste, 34127 Trieste, Italy;
| | - Amin Safa
- Experimental and Clinical Pharmacology Unit, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS National Cancer Institute, 33081 Aviano, Italy; (M.G.); (I.V.); (F.S.)
- Doctoral School in Pharmacological Sciences, University of Padua, 35131 Padova, Italy
- Department of Immunology, School of Medicine, Zabol University of Medical Sciences, Zabol 98616-15881, Iran
| | - Idris Vruzhaj
- Experimental and Clinical Pharmacology Unit, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS National Cancer Institute, 33081 Aviano, Italy; (M.G.); (I.V.); (F.S.)
- Doctoral School in Pharmacological Sciences, University of Padua, 35131 Padova, Italy
| | - Aurora Giacomin
- Department of Life Sciences, University of Trieste, 34127 Trieste, Italy;
| | - Franca Sartor
- Experimental and Clinical Pharmacology Unit, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS National Cancer Institute, 33081 Aviano, Italy; (M.G.); (I.V.); (F.S.)
| | - Giuseppe Toffoli
- Experimental and Clinical Pharmacology Unit, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS National Cancer Institute, 33081 Aviano, Italy; (M.G.); (I.V.); (F.S.)
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31
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von Bredow YM, Prochazkova P, Dvorak J, Skanta F, Trenczek TE, Bilej M, von Bredow CR. Differential expression of immunity-related genes in larval Manduca sexta tissues in response to gut and systemic infection. Front Cell Infect Microbiol 2023; 13:1258142. [PMID: 37900309 PMCID: PMC10603244 DOI: 10.3389/fcimb.2023.1258142] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2023] [Accepted: 09/18/2023] [Indexed: 10/31/2023] Open
Abstract
Introduction The midgut epithelium functions as tissue for nutrient uptake as well as physical barrier against pathogens. Additionally, it responds to pathogen contact by production and release of various factors including antimicrobial peptides, similar to the systemic innate immune response. However, if such a response is restricted to a local stimulus or if it appears in response to a systemic infection, too is a rather underexplored topic in insect immunity. We addressed the role of the midgut and the role of systemic immune tissues in the defense against gut-borne and systemic infections, respectively. Methods Manduca sexta larvae were challenged with DAP-type peptidoglycan bacteria - Bacillus thuringiensis for local gut infection and Escherichia coli for systemic stimulation. We compared the immune response to both infection models by measuring mRNA levels of four selected immunity-related genes in midgut, fat body, hematopoietic organs (HOs), and hemocytes, and determined hemolymph antimicrobial activity. Hemocytes and HOs were tested for presence and distribution of lysozyme mRNA and protein. Results The midgut and circulating hemocytes exhibited a significantly increased level of lysozyme mRNA in response to gut infection but did not significantly alter expression in response to a systemic infection. Conversely, fat body and HOs responded to both infection models by altered mRNA levels of at least one gene monitored. Most, but not all hemocytes and HO cells contain lysozyme mRNA and protein. Discussion These data suggest that the gut recruits immune-related tissues in response to gut infection whereas systemic infections do not induce a response in the midgut. The experimental approach implies a skewed cross-talk: An intestinal infection triggers immune activity in systemic immune organs, while a systemic infection does not elicit any or only a restricted immune response in the midgut. The HOs, which form and release hemocytes in larval M. sexta, i) synthesize lysozyme, and ii) respond to immune challenges by increased immune gene expression. These findings strongly suggest that they not only provide phagocytes for the cellular immune response but also synthesize humoral immune components.
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Affiliation(s)
- Yvette M. von Bredow
- Institute of Zoology and Developmental Biology, Justus-Liebig-University Gießen, Gießen, Germany
| | - Petra Prochazkova
- Laboratory of Cellular and Molecular Immunology, Institute of Microbiology of the Czech Academy of Sciences, Prague, Czechia
| | - Jiri Dvorak
- Laboratory of Cellular and Molecular Immunology, Institute of Microbiology of the Czech Academy of Sciences, Prague, Czechia
| | - Frantisek Skanta
- Laboratory of Cellular and Molecular Immunology, Institute of Microbiology of the Czech Academy of Sciences, Prague, Czechia
| | - Tina E. Trenczek
- Institute of Zoology and Developmental Biology, Justus-Liebig-University Gießen, Gießen, Germany
| | - Martin Bilej
- Laboratory of Cellular and Molecular Immunology, Institute of Microbiology of the Czech Academy of Sciences, Prague, Czechia
| | - Christoph-Rüdiger von Bredow
- Institute of Zoology and Developmental Biology, Justus-Liebig-University Gießen, Gießen, Germany
- Applied Zoology, Department of Biology, Technische Universität Dresden, Dresden, Germany
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32
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Pikov V. Vagus Nerve Stimulation and Sacral Nerve Stimulation for Inflammatory Bowel Disease: A Systematic Review. JOURNAL OF TRANSLATIONAL GASTROENTEROLOGY 2023; 1:94-100. [PMID: 38606364 PMCID: PMC11007757 DOI: 10.14218/jtg.2023.00098] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 03/15/2024]
Abstract
Background and objectives In this systematic review, we assessed the efficacy, potential mechanisms, and safety of two neuromodulation therapies in patients with inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis. The first therapy is vagus nerve stimulation (VNS) utilizing implantable or transcutaneous electrodes, and the second is sacral nerve stimulation (SNS) using implantable or percutaneous electrodes. Methods We conducted a systematic literature review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The PubMed database was comprehensively searched, and studies were rigorously assessed for inclusion and exclusion criteria. Results Our analysis encompassed five clinical studies, three on VNS and two on SNS. Most investigated studies demonstrated significant beneficial effects on IBD symptoms, including disease activity, severity of intestinal lesions, and intestinal pain. When evaluating the impact on key IBD pathophysiologies, both VNS and SNS exhibited trends toward reducing biomarkers of intestinal mucosal inflammation and mitigating sympathetic dominance. Importantly, none of the evaluated neuromodulation methods resulted in long-term adverse effects. Conclusions Cumulative evidence from the evaluated studies indicates that VNS and SNS therapies effectively alleviate IBD symptoms and may hold promise in addressing the underlying pathophysiologies of IBD, including intestinal mucosal inflammation and sympathetic dominance. Consequently, they represent valuable options for individualized IBD treatment.
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Wei Y, Huang L, Liu C, Qi M. Causal relationship between Gut Microbiota and Obstructive sleep apnea. Arch Gerontol Geriatr 2023; 113:105052. [PMID: 37148705 DOI: 10.1016/j.archger.2023.105052] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2023] [Revised: 04/12/2023] [Accepted: 04/29/2023] [Indexed: 05/08/2023]
Abstract
OBJECTIVE Although observational studies have identified relations between gut microbiota and obstructive sleep apnea (OSA), their causal links remain elusive. Hence, we aimed to investigate this causal relation using the Mendelian randomization (MR) approach. METHODS Summary-level gut microbiota data were acquired using the maximum available genome-wide association study (GWAS) from the MiBioGen consortium while obtaining summary-level OSA data using publicly available GWAS from the FinnGen Consortium. A two-sample MR analysis was used for assessing gut microbiota and OSA causal effect, using the inverse variance-weighted (IVW) approach as the primary analysis method. The results were further examined for pleiotropy and heterogeneity. Moreover, the reverse MR analysis did not find a causal relationship. RESULTS Four gut microbiota were found to have nominally significant association to OSA according to the IVW method. Among them, the family Peptostreptococcaceae (OR = 1.171, 95% CI: 1.027-1.334) and genus Coprococcus3 (OR = 1.163, 95% CI: 1.007-1.343), these two florae that may increase the risk of OSA. Family Acidaminococcaceae (OR = 0.843, 95% CI: 0.729-0.975) and genus Blautia (OR = 0.830, 95% CI: 0.708-0.972) may have an ameliorative effect on OSA. No evidence of pleiotropy or heterogeneity was found. CONCLUSIONS MR analysis indicated that a causal relation is existed between specific gut microbiota and OSA at the genetic prediction level, offering innovative perspectives into the mechanisms underlying gut microbiota-mediated OSA development.
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Affiliation(s)
- Yi Wei
- Department of Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250355, China
| | - Liyu Huang
- Department of Medical Imaging, Qingdao Hospital of Traditional Chinese Medicine, Qingdao 266014, China
| | - Chao Liu
- Department of Medical Imaging, Qingdao Hospital of Traditional Chinese Medicine, Qingdao 266014, China.
| | - Ming Qi
- Department of Primary Care, Hospital of Traditional Chinese Medicine, Qingdao 266014, China
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Ding Z, Ge W, Xu X, Xu X, Wang S, Zhang J. PER2/P65-driven glycogen synthase 1 transcription in macrophages modulates gut inflammation and pathogenesis of rectal prolapse. J Biol Chem 2023; 299:105219. [PMID: 37660913 PMCID: PMC10534228 DOI: 10.1016/j.jbc.2023.105219] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2023] [Revised: 08/12/2023] [Accepted: 08/17/2023] [Indexed: 09/05/2023] Open
Abstract
Rectal prolapse in serious inflammatory bowel disease is caused by abnormal reactions of the intestinal mucosal immune system. The circadian clock has been implicated in immune defense and inflammatory responses, but the mechanisms by which it regulates gut inflammation remain unclear. In this study, we investigate the role of the rhythmic gene Period2 (Per2) in triggering inflammation in the rectum and its contribution to the pathogenesis of rectal prolapse. We report that Per2 deficiency in mice increased susceptibility to intestinal inflammation and resulted in spontaneous rectal prolapse. We further demonstrated that PER2 was essential for the transcription of glycogen synthase 1 by interacting with the NF-κB p65. We show that the inhibition of Per2 reduced the levels of glycogen synthase 1 and glycogen synthesis in macrophages, impairing the capacity of pathogen clearance and disrupting the composition of gut microbes. Taken together, our findings identify a novel role for Per2 in regulating the capacity of pathogen clearance in macrophages and gut inflammation and suggest a potential animal model that more closely resembles human rectal prolapse.
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Affiliation(s)
- Zhao Ding
- Center for Molecular Metabolism, Nanjing University of Science & Technology, Nanjing, China
| | - Wenhao Ge
- Center for Molecular Metabolism, Nanjing University of Science & Technology, Nanjing, China
| | - Xiaodong Xu
- Center for Molecular Metabolism, Nanjing University of Science & Technology, Nanjing, China
| | - Xi Xu
- Center for Molecular Metabolism, Nanjing University of Science & Technology, Nanjing, China
| | - Shiming Wang
- Center for Molecular Metabolism, Nanjing University of Science & Technology, Nanjing, China
| | - Jianfa Zhang
- Center for Molecular Metabolism, Nanjing University of Science & Technology, Nanjing, China.
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Alonso S, Edelblum K. Metabolic regulation of γδ intraepithelial lymphocytes. DISCOVERY IMMUNOLOGY 2023; 2:kyad011. [PMID: 38179241 PMCID: PMC10766425 DOI: 10.1093/discim/kyad011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2024]
Abstract
Elucidating the relationship between cellular metabolism and T cell function has substantially advanced our understanding of how T cells are regulated in response to activation. The metabolic profiles of circulating or peripheral T cells have been well-described, yet less is known regarding how complex local microenvironments shape or modulate the bioenergetic profile of tissue-resident T lymphocytes. Intraepithelial lymphocytes expressing the γδ T cell receptor (γδ IEL) provide immunosurveillance of the intestinal epithelium to limit tissue injury and microbial invasion; however, their activation and effector responses occur independently of antigen recognition. In this review, we will summarize the current knowledge regarding γδ T cell and IEL metabolic profiles and how this informs our understanding of γδ IEL metabolism. We will also discuss the role of the gut microbiota in shaping the metabolic profile of these sentinel lymphocytes, and in turn, how these bioenergetics contribute to regulation of γδ IEL surveillance behavior and effector function. Improved understanding of the metabolic processes involved in γδ IEL homeostasis and function may yield novel strategies to amplify the protective functions of these cells in the context of intestinal health and disease.
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Affiliation(s)
- Sara Alonso
- Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Karen Edelblum
- Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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Zha C, Peng Z, Huang K, Tang K, Wang Q, Zhu L, Che B, Li W, Xu S, Huang T, Yu Y, Zhang W. Potential role of gut microbiota in prostate cancer: immunity, metabolites, pathways of action? Front Oncol 2023; 13:1196217. [PMID: 37265797 PMCID: PMC10231684 DOI: 10.3389/fonc.2023.1196217] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2023] [Accepted: 05/04/2023] [Indexed: 06/03/2023] Open
Abstract
The gut microbiota helps to reveal the relationship between diseases, but the role of gut microbiota in prostate cancer (PCa) is still unclear. Recent studies have found that the composition and abundance of specific gut microbiota are significantly different between PCa and non-PCa, and the gut microbiota may have common and unique characteristics between different diseases. Intestinal microorganisms are affected by various factors and interact with the host in a variety of ways. In the complex interaction model, the regulation of intestinal microbial metabolites and the host immune system is particularly important, and they play a key role in maintaining the ecological balance of intestinal microorganisms and metabolites. However, specific changes in the composition of intestinal microflora may promote intestinal mucosal immune imbalance, leading to the formation of tumors. Therefore, this review analyzes the immune regulation of intestinal flora and the production of metabolites, as well as their effects and mechanisms on tumors, and briefly summarizes that specific intestinal flora can play an indirect role in PCa through their metabolites, genes, immunity, and pharmacology, and directly participate in the occurrence, development, and treatment of tumors through bacterial and toxin translocation. We also discussed markers of high risk PCa for intestinal microbiota screening and the possibility of probiotic ingestion and fecal microbiota transplantation, in order to provide better treatment options for clinic patients. Finally, after summarizing a number of studies, we found that changes in immunity, metabolites.
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Affiliation(s)
- Cheng Zha
- Department of Urology, The Affiliated Hospital of Guizhou Medical University, Guiyang, China
| | - Zheng Peng
- Department of Urology, The Affiliated Hospital of Guizhou Medical University, Guiyang, China
| | - Kunyuan Huang
- Department of Urology, The Affiliated Hospital of Guizhou Medical University, Guiyang, China
| | - Kaifa Tang
- Department of Urology, The Affiliated Hospital of Guizhou Medical University, Guiyang, China
- Department of Urology & Andrology, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, China
| | - Qiang Wang
- Department of Urology, The Affiliated Hospital of Guizhou Medical University, Guiyang, China
| | - Lihua Zhu
- Department of Urology, The Affiliated Hospital of Guizhou Medical University, Guiyang, China
| | - Bangwei Che
- Department of Urology, The Affiliated Hospital of Guizhou Medical University, Guiyang, China
| | - Wei Li
- Department of Urology, The Affiliated Hospital of Guizhou Medical University, Guiyang, China
| | - Shenghan Xu
- Department of Urology, The Affiliated Hospital of Guizhou Medical University, Guiyang, China
| | - Tao Huang
- Department of Urology, The Affiliated Hospital of Guizhou Medical University, Guiyang, China
| | - Ying Yu
- Department of Urology, The Affiliated Hospital of Guizhou Medical University, Guiyang, China
| | - Wenjun Zhang
- Department of Urology, The Affiliated Hospital of Guizhou Medical University, Guiyang, China
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Zhang W, Teng M, Yan J, Chen L. Study effect and mechanism of levofloxacin on the neurotoxicity of Rana nigromaculata tadpoles exposed to imidacloprid based on the microbe-gut-brain axis. THE SCIENCE OF THE TOTAL ENVIRONMENT 2023; 872:162098. [PMID: 36764551 DOI: 10.1016/j.scitotenv.2023.162098] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/07/2022] [Revised: 01/25/2023] [Accepted: 02/04/2023] [Indexed: 06/18/2023]
Abstract
Aquatic organisms may be simultaneously exposed to antibiotics and pesticides. After levofloxacin (LVFX), imidacloprid (IMI) exposure and co-exposure at environmental levels, we found LVFX and IMI had antagonistic effect on the neurotoxicity of tadpoles. IMI-induced neurotoxicity on tadpoles can be explained by oxidative stress and hormone levels in some degree. By regulating ornithine, l-asparagine, putrescine and tryptamine in the intestine, LVFX affected glutathione metabolism, arginine and proline metabolism, alanine, aspartate and glutamate metabolism, tyrosine metabolism and aminoacyl tRNA biosynthesis, so then eased the neurotoxicity caused by IMI. More interestingly, Fusobacteriota and Cetobacterium might play an important role on easing the neurotoxicity caused by IMI. In addition, LVFX might have a laxation effect on the increased relative abundance of Bacteroidota caused by IMI. In conclusion, IMI not only affected oxidative stress and hormone levels in the brain, but also affected the synthesis of neurotransmitters in the intestine by regulating intestinal microbiota. In LVFX and IMI co-exposed groups, LVFX alleviated the neurotoxicity caused by IMI through regulating the intestinal microbiota, showing as an antagonistic effect. Our results provided a new perspective for aquatic ecological risk assessment under co-exposure of antibiotics and pesticides.
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Affiliation(s)
- Wenjun Zhang
- Key Laboratory of Integrated Regulation and Resources Development on Shallow Lakes of Ministry of Education, College of Environment, Hohai University, Nanjing 210098, China.
| | - Miaomiao Teng
- State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing 100012, China
| | - Jin Yan
- National and Local Joint Engineering Laboratory of Municipal Sewage Resource Utilization Technology, School of Environmental Science and Engineering, Suzhou University of Science and Technology, Suzhou 215009, China
| | - Li Chen
- Human Nutrition Program, Department of Human Sciences, The Ohio State University, Columbus, OH 43210, USA
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Zhao L, Wang Y, Jaganathan A, Sun Y, Ma N, Li N, Han X, Sun X, Yi H, Fu S, Han F, Li X, Xiao K, Walsh MJ, Zeng L, Zhou M, Cheung KL. BRD4-PRC2 represses transcription of T-helper 2-specific negative regulators during T-cell differentiation. EMBO J 2023; 42:e111473. [PMID: 36719036 PMCID: PMC10015369 DOI: 10.15252/embj.2022111473] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2022] [Revised: 12/26/2022] [Accepted: 01/11/2023] [Indexed: 02/01/2023] Open
Abstract
BRD4 is a well-recognized transcriptional activator, but how it regulates gene transcriptional repression in a cell type-specific manner has remained elusive. In this study, we report that BRD4 works with Polycomb repressive complex 2 (PRC2) to repress transcriptional expression of the T-helper 2 (Th2)-negative regulators Foxp3 and E3-ubiqutin ligase Fbxw7 during lineage-specific differentiation of Th2 cells from mouse primary naïve CD4+ T cells. Brd4 binds to the lysine-acetylated-EED subunit of the PRC2 complex via its second bromodomain (BD2) to facilitate histone H3 lysine 27 trimethylation (H3K27me3) at target gene loci and thereby transcriptional repression. We found that Foxp3 represses transcription of Th2-specific transcription factor Gata3, while Fbxw7 promotes its ubiquitination-directed protein degradation. BRD4-mediated repression of Foxp3 and Fbxw7 in turn promotes BRD4- and Gata3-mediated transcriptional activation of Th2 cytokines including Il4, Il5, and Il13. Chemical inhibition of the BRD4 BD2 induces transcriptional de-repression of Foxp3 and Fbxw7, and thus transcriptional downregulation of Il4, Il5, and Il13, resulting in inhibition of Th2 cell lineage differentiation. Our study presents a previously unappreciated mechanism of BRD4's role in orchestrating a Th2-specific transcriptional program that coordinates gene repression and activation, and safeguards cell lineage differentiation.
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Affiliation(s)
- Li Zhao
- Institute of Epigenetic Medicine, First Hospital of Jilin UniversityChangchunChina
| | - Yiqi Wang
- Institute of Epigenetic Medicine, First Hospital of Jilin UniversityChangchunChina
| | - Anbalagan Jaganathan
- Department of Pharmacological SciencesIcahn School of Medicine at Mount SinaiNew YorkNYUSA
| | - Yifei Sun
- Department of Pharmacological SciencesIcahn School of Medicine at Mount SinaiNew YorkNYUSA
| | - Ning Ma
- Institute of Epigenetic Medicine, First Hospital of Jilin UniversityChangchunChina
| | - Ning Li
- The Institute of Genetics and Cytology, Northeast Normal UniversityChangchunChina
| | - Xinye Han
- Institute of Epigenetic Medicine, First Hospital of Jilin UniversityChangchunChina
| | - Xueying Sun
- Institute of Epigenetic Medicine, First Hospital of Jilin UniversityChangchunChina
| | - Huanfa Yi
- Institute of Epigenetic Medicine, First Hospital of Jilin UniversityChangchunChina
| | - Shibo Fu
- Institute of Epigenetic Medicine, First Hospital of Jilin UniversityChangchunChina
| | - Fangbin Han
- Institute of Epigenetic Medicine, First Hospital of Jilin UniversityChangchunChina
| | - Xue Li
- Department of ChemistryMichigan State UniversityEast LansingMIUSA
| | - Kunhong Xiao
- Center for Proteomics & Artificial Intelligence and Center for Clinical Mass SpectrometryAllegheny Health Network Cancer InstitutePittsburghPAUSA
- Department of Pharmacology and Chemical Biology, School of MedicineUniversity of PittsburghPittsburghPAUSA
| | - Martin J Walsh
- Department of Pharmacological SciencesIcahn School of Medicine at Mount SinaiNew YorkNYUSA
| | - Lei Zeng
- Institute of Epigenetic Medicine, First Hospital of Jilin UniversityChangchunChina
| | - Ming‐Ming Zhou
- Department of Pharmacological SciencesIcahn School of Medicine at Mount SinaiNew YorkNYUSA
| | - Ka Lung Cheung
- Department of Pharmacological SciencesIcahn School of Medicine at Mount SinaiNew YorkNYUSA
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Yoshikawa S, Taniguchi K, Sawamura H, Ikeda Y, Tsuji A, Matsuda S. Advantageous tactics with certain probiotics for the treatment of graft-versus-host-disease after hematopoietic stem cell transplantation. World J Hematol 2023; 10:15-24. [DOI: 10.5315/wjh.v10.i2.15] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2022] [Revised: 11/03/2022] [Accepted: 11/23/2022] [Indexed: 01/17/2023] Open
Abstract
Hematopoietic stem cell transplantation (HSCT) becomes a standard form of cellular therapy for patients with malignant diseases. HSCT is the first-choice of immunotherapy, although HSCT can be associated with many complications such as graft-versus-host disease (GVHD) which is a major cause of morbidity and mortality after allogeneic HSCT. It has been shown that certain gut microbiota could exert protective and/or regenerative immunomodulatory effects by the production of short-chain fatty acids (SCFAs) such as butyrate in the experimental models of GVHD after allogeneic HSCT. Loss of gut commensal bacteria which can produce SCFAs may worsen dysbiosis, increasing the risk of GVHD. Expression of G-protein coupled receptors such as GPR41 seems to be upre-gulated in the presence of commensal bacteria, which might be associated with the biology of regulatory T cells (Tregs). Treg cells are a suppressive subset of CD4 positive T lymphocytes implicated in the prevention of GVHD after allogeneic HSCT. Here, we discuss the current findings of the relationship between the modification of gut microbiota and the GVHD-related immunity, which suggested that tactics with certain probiotics for the beneficial symbiosis in gut-immune axis might lead to the elevation of safety in the allogeneic HSCT.
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Affiliation(s)
- Sayuri Yoshikawa
- Food Science and Nutrition, Nara Women's University, Nara 630-8506, Japan
| | - Kurumi Taniguchi
- Food Science and Nutrition, Nara Women's University, Nara 630-8506, Japan
| | - Haruka Sawamura
- Food Science and Nutrition, Nara Women's University, Nara 630-8506, Japan
| | - Yuka Ikeda
- Food Science and Nutrition, Nara Women's University, Nara 630-8506, Japan
| | - Ai Tsuji
- Food Science and Nutrition, Nara Women's University, Nara 630-8506, Japan
| | - Satoru Matsuda
- Food Science and Nutrition, Nara Women's University, Nara 630-8506, Japan
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Chen L, Ruan G, Cheng Y, Yi A, Chen D, Wei Y. The role of Th17 cells in inflammatory bowel disease and the research progress. Front Immunol 2023; 13:1055914. [PMID: 36700221 PMCID: PMC9870314 DOI: 10.3389/fimmu.2022.1055914] [Citation(s) in RCA: 66] [Impact Index Per Article: 33.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Accepted: 11/28/2022] [Indexed: 01/11/2023] Open
Abstract
Th17 cells play an important role in the abnormal immune response in inflammatory bowel disease (IBD) and are involved in the development and progression of inflammation and fibrosis. An increasing amount of data has shown that gut microbes are important parts of intestinal immunity and regulators of Th17 cellular immunity. Th17 cell differentiation is regulated by intestinal bacteria and cytokines, and Th17 cells regulate the intestinal mucosal immune microenvironment by secreting cytokines, such as IL-17, IL-21, and IL-26. Solid evidence showed that, regarding the treatment of IBD by targeting Th17 cells, the therapeutic effect of different biological agents varies greatly. Fecal bacteria transplantation (FMT) in the treatment of IBD has been a popular research topic in recent years and is safe and effective with few side effects. To further understand the role of Th17 cells in the progression of IBD and associated therapeutic prospects, this review will discuss the progress of related research on Th17 cells in IBD by focusing on the interaction and immune regulation between Th17 cells and gut microbiota.
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Affiliation(s)
| | | | | | | | | | - Yanling Wei
- *Correspondence: Yanling Wei, ; Dongfeng Chen,
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Abstract
Thymic stromal lymphopoietin (TSLP) is a pleiotropic cytokine that acts on multiple cell lineages, including dendritic cells, T cells, B cells, neutrophils, mast cells, eosinophils and innate lymphoid cells, affecting their maturation, survival and recruitment. It is best known for its role in promoting type 2 immune responses such as in allergic diseases and, in 2021, a monoclonal antibody targeting TSLP was approved for the treatment of severe asthma. However, it is now clear that TSLP has many other important roles in a variety of settings. Indeed, several genetic variants for TSLP are linked to disease severity, and chromosomal alterations in TSLP are common in certain cancers, indicating important roles of TSLP in disease. In this Review, we discuss recent advances in TSLP biology, highlighting how it regulates the tissue environment not only in allergic disease but also in infectious diseases, inflammatory diseases and cancer. Encouragingly, therapies targeting the TSLP pathway are being actively pursued for several diseases.
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Affiliation(s)
- Risa Ebina-Shibuya
- Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Warren J Leonard
- Laboratory of Molecular Immunology, Immunology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
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Wang EJ, Wu MY, Ren ZY, Zheng Y, Ye RD, TAN CSH, Wang Y, Lu JH. Targeting macrophage autophagy for inflammation resolution and tissue repair in inflammatory bowel disease. BURNS & TRAUMA 2023; 11:tkad004. [PMID: 37152076 PMCID: PMC10157272 DOI: 10.1093/burnst/tkad004] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/16/2022] [Revised: 12/22/2022] [Accepted: 01/16/2023] [Indexed: 05/09/2023]
Abstract
Inflammatory bowel disease (IBD) is a chronic, non-specific, recurrent inflammatory disease, majorly affecting the gastrointestinal tract. Due to its unclear pathogenesis, the current therapeutic strategy for IBD is focused on symptoms alleviation. Autophagy is a lysosome-mediated catabolic process for maintaining cellular homeostasis. Genome-wide association studies and subsequent functional studies have highlighted the critical role of autophagy in IBD via a number of mechanisms, including modulating macrophage function. Macrophages are the gatekeepers of intestinal immune homeostasis, especially involved in regulating inflammation remission and tissue repair. Interestingly, many autophagic proteins and IBD-related genes have been revealed to regulate macrophage function, suggesting that macrophage autophagy is a potentially important process implicated in IBD regulation. Here, we have summarized current understanding of macrophage autophagy function in pathogen and apoptotic cell clearance, inflammation remission and tissue repair regulation in IBD, and discuss how this knowledge can be used as a strategy for IBD treatment.
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Affiliation(s)
- Er-jin Wang
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR, 999078, China
| | - Ming-Yue Wu
- Center for Metabolic Liver Diseases and Center for Cholestatic Liver Diseases, Department of Gastroenterology, The First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, 400038, China
| | - Zheng-yu Ren
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR, 999078, China
| | - Ying Zheng
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR, 999078, China
| | - Richard D Ye
- Kobilka Institute of Innovative Drug Discovery, School of Life and Health Sciences, The Chinese University of Hong Kong, Shenzhen, 518172, China
| | - Chris Soon Heng TAN
- Department of Chemistry, College of Science, Southern University of Science and Technology, Shenzhen, 518055, China
| | - Yitao Wang
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR, 999078, China
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Liang H, Zhang L, Hoden B, Qu B, Derubeis D, Song X, Zhang D. Delineating the Role of Toll-Like Receptors in Inflammatory Bowel Disease. Methods Mol Biol 2023; 2700:221-228. [PMID: 37603184 DOI: 10.1007/978-1-0716-3366-3_13] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/22/2023]
Abstract
Toll-like receptors (TLRs) recognize altered gut microbiota triggering an immune response. These responses play a critical role in the pathogenesis and treatment of inflammatory bowel disease (IBD). IBD is characterized by inflammation of the intestinal tracts as in Crohn's disease and ulcerative colitis. However, one challenge in determining the role of a specific TLR in IBD and its underlying mechanism is disparity. Variance in age, gender, race, and ethnicity shows a dramatic difference in the disease incidence, severity, and response to treatment. Delineating the role of TLRs in IBD relies on both a knockout mouse and a disease model. Here, we describe a detailed protocol on how to use nearly identical genetic backgrounds of TLR wild-type and knockout littermate mice in a dextran sodium sulfate (DSS)-induced colitis model.
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Affiliation(s)
- Hongbin Liang
- Center for Infectious and Inflammatory Diseases, Institute of Biosciences and Technology, Texas A&M University, Houston, TX, USA
| | - Lin Zhang
- Center for Infectious and Inflammatory Diseases, Institute of Biosciences and Technology, Texas A&M University, Houston, TX, USA
| | - Bettina Hoden
- Center for Infectious and Inflammatory Diseases, Institute of Biosciences and Technology, Texas A&M University, Houston, TX, USA
| | - Bo Qu
- Department of Gastroenterology, The Second Affiliated Hospital, Harbin Medical University, Harbin, China
| | - David Derubeis
- Center for Infectious and Inflammatory Diseases, Institute of Biosciences and Technology, Texas A&M University, Houston, TX, USA
| | - Xiaotong Song
- Center for Infectious and Inflammatory Diseases, Institute of Biosciences and Technology, Texas A&M University, Houston, TX, USA.
| | - Dekai Zhang
- Center for Infectious and Inflammatory Diseases, Institute of Biosciences and Technology, Texas A&M University, Houston, TX, USA.
- Department of Translational Medical Sciences, College of Medicine, Texas A&M University, Houston, TX, USA.
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Tong Y, Yu C, Chen S, Zhang X, Yang Z, Wang T. Trans-anethole exerts protective effects on lipopolysaccharide-induced acute jejunal inflammation of broilers via repressing NF-κB signaling pathway. Poult Sci 2022; 102:102397. [PMID: 36565631 PMCID: PMC9801195 DOI: 10.1016/j.psj.2022.102397] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2022] [Revised: 11/29/2022] [Accepted: 12/05/2022] [Indexed: 12/13/2022] Open
Abstract
This study aimed to explore the effects of trans-anethole (TA) on lipopolysaccharide (LPS)-induced acute jejunal inflammation model of broilers. A total of 160 one-day-old broilers (male; Arbor Acres) were randomly allocated into four treatment groups with 8 replicates of 5 birds each. On d 20, the dose of 5 mg/kg body weight LPS solution and the equal amount of sterile saline were intraperitoneally injected into LPS-challenged and unchallenged broilers, respectively. Compared with the control group, LPS decreased (P < 0.05) the villus height (VH) and the ratio of villus height to crypt depth (VCR) but increased (P < 0.05) the crypt depth (CD), meanwhile, enhanced (P < 0.01) the levels of interleukin-6 (IL-6), interleukin-1beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) but decreased (P < 0.01) the level of interleukin-10 (IL-10). The group supplemented with 600 mg/kg of TA had lower (P < 0.01) CD and higher (P < 0.01) VCR than the LPS group. TA increased (P < 0.01) the level of IL-10 and decreased (P < 0.01) the level of IL-1β. The mRNA expression levels of IL-6, nuclear factor kappa B (NF-κB), TNF-α were up-regulated (P < 0.05) and the levels of IL-10 and inhibitor of NF-κB alpha (IκBα) were down-regulated (P < 0.05) by LPS as compared with the control group. TA down-regulated (P < 0.05) the increased mRNA expression levels of genes caused by LPS, as well as up-regulated (P < 0.05) the levels of IL-10 and IκBα. Furthermore, LPS down-regulated (P < 0.05) and up-regulated (P < 0.05) the protein expression levels of IκBα and NF-κB p65, respectively. TA up-regulated (P < 0.05) the level of IκBα and down-regulated (P < 0.05) the level of NF-κB p65. The conclusion of this study is that TA could exert protective effect on the LPS-induced acute jejunal inflammation of broilers via repressing the activation of NF-κB and the 600 mg/kg is the optimal dose against LPS-induced acute jejunal inflammation of broilers.
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Affiliation(s)
- Yichun Tong
- College of Animal Sciences and Technology, Nanjing Agricultural University, Nanjing, 210095 Jiangsu, PR China
| | - Caiyun Yu
- College of Animal Sciences and Technology, Nanjing Agricultural University, Nanjing, 210095 Jiangsu, PR China
| | - Shun Chen
- College of Animal Sciences and Technology, Nanjing Agricultural University, Nanjing, 210095 Jiangsu, PR China
| | - Xianglei Zhang
- College of Animal Sciences and Technology, Nanjing Agricultural University, Nanjing, 210095 Jiangsu, PR China
| | - Zaibin Yang
- College of Animal Sciences and Technology, Shandong Agricultural University, Tai'an, 271018 Shandong, PR China
| | - Tian Wang
- College of Animal Sciences and Technology, Nanjing Agricultural University, Nanjing, 210095 Jiangsu, PR China,Corresponding author:
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Subki AH, Bokhary MI, Alandijani SA, Aljehani MA, Alharbi AW, Alzahrani M, Almuhammadi SS, Albeirouti BT, Abduljabar MA, Danese S. Resolved Hypereosinophilic Syndrome and Immune Thrombocytopenic Purpura in Ulcerative Colitis Patients Post Colectomy: A Case Series and Literature Review. J Inflamm Res 2022; 15:6373-6380. [PMID: 36439947 PMCID: PMC9697402 DOI: 10.2147/jir.s365094] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Accepted: 11/03/2022] [Indexed: 09/10/2024] Open
Abstract
Introduction Hypereosinophilic syndrome (HES) and immune thrombocytopenic purpura (ITP) have been reported to co-occur with ulcerative colitis (UC). However, the exact pathogenic mechanisms of their occurrence remain elusive. In this article, we aim to describe two cases of UC patients who developed refractory HES and ITP and elaborate on their potential pathogenesis. Case Study We report two middle-aged patients diagnosed with UC. The first patient developed HES that was refractory to conventional medical therapy of idiopathic HES, and the second developed refractory ITP that failed steroid and immunosuppressive therapy. Both conditions improved considerably following colectomy, suggesting they are of a reactive rather than idiopathic nature. Conclusion In patients with UC and refractory comorbid HES or ITP, the reactive nature of these comorbidities should be taken into consideration, and colectomy, therefore, should be considered if clinically indicated.
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Affiliation(s)
- Ahmed Hussein Subki
- Department of Internal Medicine, King Faisal Specialist Hospital & Research Centre, Jeddah, Saudi Arabia
| | - Manal Ismail Bokhary
- Department of Internal Medicine, King Faisal Specialist Hospital & Research Centre, Jeddah, Saudi Arabia
| | | | | | - Ahmed Wasel Alharbi
- Department of Internal Medicine, King Faisal Specialist Hospital & Research Centre, Jeddah, Saudi Arabia
| | - May Alzahrani
- Department of Internal Medicine, King Faisal Specialist Hospital & Research Centre, Jeddah, Saudi Arabia
| | | | - Bassim Tahseen Albeirouti
- Adult Hematology/Bone Marrow Transplant (BMT) Section, Department of Oncology, King Faisal Specialist Hospital and Research Centre, Jeddah, Saudi Arabia
| | | | - Silvio Danese
- Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital and Vita-Salute San Raffaele University, Milan, Italy
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Morphological Assessment and Biomarkers of Low-Grade, Chronic Intestinal Inflammation in Production Animals. Animals (Basel) 2022; 12:ani12213036. [PMID: 36359160 PMCID: PMC9654368 DOI: 10.3390/ani12213036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2022] [Revised: 10/27/2022] [Accepted: 10/28/2022] [Indexed: 11/09/2022] Open
Abstract
Simple Summary Production animals are continuously exposed to environmental and dietary factors that might induce a state of low-grade, chronic intestinal inflammation. This condition compromises the productive performance and well-fare of these animals, requiring studies to understand what causes it and to develop control strategies. An intestinal inflammatory process is generally associated with alterations in the structure and functionality of its wall, resulting in the release of cellular components into the blood and/or feces. These components can act as biomarkers, i.e., they are measured to identify and quantify an inflammatory process without requiring invasive methods. In this review we discuss the mechanisms of low-grade inflammation, its effects on animal production and sustainability, and the identification of biomarkers that could provide early diagnosis of this process and support studies of useful interventional strategies. Abstract The complex interaction between the intestinal mucosa, the gut microbiota, and the diet balances the host physiological homeostasis and is fundamental for the maximal genetic potential of production animals. However, factors such as chemical and physical characteristics of the diet and/or environmental stressors can continuously affect this balance, potentially inducing a state of chronic low-grade inflammation in the gut, where inflammatory parameters are present and demanding energy, but not in enough intensity to provoke clinical manifestations. It’s vital to expand the understanding of inflammation dynamics and of how they compromise the function activity and microscopic morphology of the intestinal mucosa. These morphometric alterations are associated with the release of structural and functional cellular components into the feces and the blood stream creating measurable biomarkers to track this condition. Moreover, the identification of novel, immunometabolic biomarkers can provide dynamic and predictors of low-grade chronic inflammation, but also provide indicators of successful nutritional or feed additive intervention strategies. The objective of this paper is to review the mechanisms of low-grade inflammation, its effects on animal production and sustainability, and the biomarkers that could provide early diagnosis of this process and support studies of useful interventional strategies.
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Lactobacillus fermentum (MTCC-5898) based fermented whey renders prophylactic action against colitis by strengthening the gut barrier function and maintaining immune homeostasis. Microb Pathog 2022; 173:105887. [DOI: 10.1016/j.micpath.2022.105887] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2022] [Revised: 11/07/2022] [Accepted: 11/14/2022] [Indexed: 11/18/2022]
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Martin-Gallausiaux C, Garcia-Weber D, Lashermes A, Larraufie P, Marinelli L, Teixeira V, Rolland A, Béguet-Crespel F, Brochard V, Quatremare T, Jamet A, Doré J, Gray-Owen SD, Blottière HM, Arrieumerlou C, Lapaque N. Akkermansia muciniphila upregulates genes involved in maintaining the intestinal barrier function via ADP-heptose-dependent activation of the ALPK1/TIFA pathway. Gut Microbes 2022; 14:2110639. [PMID: 36036242 PMCID: PMC9427033 DOI: 10.1080/19490976.2022.2110639] [Citation(s) in RCA: 43] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
The commensal bacteria that make up the gut microbiota impact the health of their host on multiple levels. In particular, the interactions taking place between the microbe-associated molecule patterns (MAMPs) and pattern recognition receptors (PRRs), expressed by intestinal epithelial cells (IECs), are crucial for maintaining intestinal homeostasis. While numerous studies showed that TLRs and NLRs are involved in the control of gut homeostasis by commensal bacteria, the role of additional innate immune receptors remains unclear. Here, we seek for novel MAMP-PRR interactions involved in the beneficial effect of the commensal bacterium Akkermansia muciniphila on intestinal homeostasis. We show that A. muciniphila strongly activates NF-κB in IECs by releasing one or more potent activating metabolites into the microenvironment. By using drugs, chemical and gene-editing tools, we found that the released metabolite(s) enter(s) epithelial cells and activate(s) NF-κB via an ALPK1, TIFA and TRAF6-dependent pathway. Furthermore, we show that the released molecule has the biological characteristics of the ALPK1 ligand ADP-heptose. Finally, we show that A. muciniphila induces the expression of the MUC2, BIRC3 and TNFAIP3 genes involved in the maintenance of the intestinal barrier function and that this process is dependent on TIFA. Altogether, our data strongly suggest that the commensal A. muciniphila promotes intestinal homeostasis by activating the ALPK1/TIFA/TRAF6 axis, an innate immune pathway exclusively described so far in the context of Gram-negative bacterial infections.
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Affiliation(s)
| | | | - Amandine Lashermes
- INRAE, AgroParisTech, Micalis Institute, Université Paris-Saclay, Jouy-en-Josas, France
| | - Pierre Larraufie
- INRAE, AgroParisTech, Micalis Institute, Université Paris-Saclay, Jouy-en-Josas, France
| | - Ludovica Marinelli
- INRAE, AgroParisTech, Micalis Institute, Université Paris-Saclay, Jouy-en-Josas, France
| | - Veronica Teixeira
- INSERM, Institut Cochin, Université de Paris Cité, CNRS, Paris, France
| | - Alice Rolland
- INRAE, AgroParisTech, Micalis Institute, Université Paris-Saclay, Jouy-en-Josas, France
| | | | - Vincent Brochard
- INRAE, AgroParisTech, Micalis Institute, Université Paris-Saclay, Jouy-en-Josas, France
| | - Timothé Quatremare
- INRAE, AgroParisTech, Micalis Institute, Université Paris-Saclay, Jouy-en-Josas, France
| | - Alexandre Jamet
- INRAE, AgroParisTech, Micalis Institute, Université Paris-Saclay, Jouy-en-Josas, France
| | - Joël Doré
- INRAE, AgroParisTech, Micalis Institute, Université Paris-Saclay, Jouy-en-Josas, France
| | - Scott D. Gray-Owen
- Department of Molecular Genetics, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Hervé M. Blottière
- INRAE, AgroParisTech, Micalis Institute, Université Paris-Saclay, Jouy-en-Josas, France
| | | | - Nicolas Lapaque
- INRAE, AgroParisTech, Micalis Institute, Université Paris-Saclay, Jouy-en-Josas, France,CONTACT Nicolas Lapaque INRAE-MICALIS UMR1319, Bat 442, Domaine de Vilvert78350Jouy-en-Josas, France
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Lu Q, Li J, Ding P, Mao T, Shi L, Sun Z, Tan X, Jiang H, Dong J, Li Y, Yang X, Shi R. Qingchang Wenzhong Decoction Alleviates DSS-Induced Inflammatory Bowel Disease by Inhibiting M1 Macrophage Polarization In Vitro and In Vivo. BIOMED RESEARCH INTERNATIONAL 2022; 2022:9427076. [PMID: 36060126 PMCID: PMC9436576 DOI: 10.1155/2022/9427076] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/15/2022] [Revised: 07/28/2022] [Accepted: 08/03/2022] [Indexed: 12/02/2022]
Abstract
Background An imbalance of macrophage M1/M2 polarization significantly influences the pathogenesis of inflammatory bowel disease. Qingchang Wenzhong decoction (QCWZD) has a proven therapeutic effect on patients with inflammatory bowel disease (IBD) and can significantly inhibit the inflammatory response in mice with colitis. However, its effect on macrophages during IBD treatment remains nebulous. Aim of the Study. Explore the mechanism underlying QCWZD effects in a dextran sulfate sodium (DSS)-induced colitis mouse model in vivo and RAW264.7 cell in vitro by observing macrophage polarization dynamics. Methods The main active components of QCWZD were determined using high-performance liquid chromatography. Surface marker expression on M1-type macrophages was analyzed using flow cytometry and immunofluorescence. The effect on inducible nitric oxide synthase (iNOS), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) released by M1 type macrophages was determined using ELSA and RT-PCR. The expression of key proteins in the JAK2/STAT3 signaling pathway was analyzed using western blotting. QCWZD cytotoxicity in macrophages was measured using CCK8 and Annexin V-FITC/PI assays. Results The main active components of QCWZD were berberine chloride, coptisine chloride, epiberberine chloride, gallic acid, ginsenoside Rg1, ginsenoside Rb1, indigo, indirubin, notoginsenoside R1, palmatine chloride, and 6-curcumin. QCWZD markedly alleviated DSS-induced colitis in mice, as revealed by the rescued weight loss and disease activity index, attenuated the colonic shortening and mucosal injury associated with the inhibition of M1 macrophage polarization and expression of related cytokines, such as IL-6 and TNF-α, in vivo and in vitro. Furthermore, QCWZD decreased the iNOS, JAK2, and STAT3 levels in vivo and in vitro, regulating the JAK2/STAT3 signaling pathway. Conclusion QCWZD administration improves intestinal inflammation by inhibiting M1 macrophage polarization. The JAK2/STAT3 signaling pathway may mediate the effects of QCWZD on M1 macrophage polarization in colitis treatment. This study presents a novel macrophage-mediated therapeutic strategy for the treatment of IBD.
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Affiliation(s)
- Qiongqiong Lu
- Graduate School, Beijing University of Chinese Medicine, Beijing, China
- Department of Gastroenterology, Chongqing Traditional Chinese Medicine Hospital, Chongqing, China
| | - Junxiang Li
- Department of Gastroenterology, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Panghua Ding
- Graduate School, Beijing University of Chinese Medicine, Beijing, China
| | - Tangyou Mao
- Department of Gastroenterology, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Lei Shi
- Department of Gastroenterology, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Zhongmei Sun
- Graduate School, Beijing University of Chinese Medicine, Beijing, China
| | - Xiang Tan
- Graduate School, Beijing University of Chinese Medicine, Beijing, China
| | - Hui Jiang
- Graduate School, Beijing University of Chinese Medicine, Beijing, China
| | - Junying Dong
- Graduate School, Beijing University of Chinese Medicine, Beijing, China
| | - Yalan Li
- Graduate School, Beijing University of Chinese Medicine, Beijing, China
| | - Xiaojun Yang
- Department of Gastroenterology, Chongqing Traditional Chinese Medicine Hospital, Chongqing, China
| | - Rui Shi
- Department of Gastroenterology, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China
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50
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Yu H, Mi C, Wang Q, Dai G, Zhang T, Zhang G, Xie K, Zhao Z. Long noncoding RNA profiling reveals that LncRNA BTN3A2 inhibits the host inflammatory response to Eimeria tenella infection in chickens. Front Immunol 2022; 13:891001. [PMID: 36091044 PMCID: PMC9452752 DOI: 10.3389/fimmu.2022.891001] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2022] [Accepted: 08/05/2022] [Indexed: 02/02/2023] Open
Abstract
Coccidiosis is a widespread parasitic disease that causes serious economic losses to the poultry industry every year. Long noncoding RNAs (lncRNAs) play important roles in transcriptional regulation and are involved in a variety of diseases and immune responses. However, the lncRNAs associated with Eimeria tenella (E. tenella) resistance have not been identified in chickens. In addition, the expression profiles and functions of lncRNAs during E. tenella infection remain unclear. In the present study, high-throughput sequencing was applied to identify lncRNAs in chicken cecal tissues from control (JC), resistant (JR), and susceptible (JS) groups on day 4.5 post-infection (pi), and functional tests were performed. A total of 564 lncRNAs were differentially expressed, including 263 lncRNAs between the JS and JC groups, 192 between the JR and JS groups, and 109 between the JR and JC groups. Functional analyses indicated that these differentially expressed lncRNAs were involved in pathways related to E. tenella infection, including the NF-kappa B signaling, B cell receptor signaling and natural killer cell-mediated cytotoxicity pathways. Moreover, through cis regulation network analysis of the differentially expressed lncRNAs, we found that a novel lncRNA termed lncRNA BTN3A2 was significantly increased in both cecum tissue and DF-1 cells after coccidia infection or sporozoite stimulation. Functional test data showed that the overexpression of lncRNA BTN3A2 reduced the production of inflammatory cytokines, including IL-6, IL-1β, TNF-α and IL-8, while lncRNA BTN3A2 knockdown promoted the production of these inflammatory cytokines. Taken together, this study identify the differentially expressed lncRNAs during E. tenella infection in chickens for the first time and provide the direct evidence that lncRNA BTN3A2 regulates the host immune response to coccidia infection.
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Affiliation(s)
- Hailiang Yu
- College of Animal Science and Technology, Yangzhou University, Yangzhou, China
| | - Changhao Mi
- College of Animal Science and Technology, Yangzhou University, Yangzhou, China
| | - Qi Wang
- College of Animal Science and Technology, Yangzhou University, Yangzhou, China
| | - Guojun Dai
- College of Animal Science and Technology, Yangzhou University, Yangzhou, China
- *Correspondence: Guojun Dai,
| | - Tao Zhang
- College of Animal Science and Technology, Yangzhou University, Yangzhou, China
| | - Genxi Zhang
- College of Animal Science and Technology, Yangzhou University, Yangzhou, China
| | - Kaizhou Xie
- College of Animal Science and Technology, Yangzhou University, Yangzhou, China
| | - Zhenhua Zhao
- Poultry Institute, Chinese Academy of Agricultural Sciences, Yangzhou, China
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