Reference Citation Analysis: Find an Article, Find a Category, Find a Journal, Find a Scholar

For: Tawiah A, Cornick S, Moreau F, Gorman H, Kumar M, Tiwari S, Chadee K. High MUC2 Mucin Expression and Misfolding Induce Cellular Stress, Reactive Oxygen Production, and Apoptosis in Goblet Cells. Am J Pathol 2018;188:1354-1373. [PMID: 29545196 DOI: 10.1016/j.ajpath.2018.02.007] [Citation(s) in RCA: 50] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/22/2017] [Revised: 02/06/2018] [Accepted: 02/20/2018] [Indexed: 12/20/2022]

For:	Tawiah A, Cornick S, Moreau F, Gorman H, Kumar M, Tiwari S, Chadee K. High MUC2 Mucin Expression and Misfolding Induce Cellular Stress, Reactive Oxygen Production, and Apoptosis in Goblet Cells. Am J Pathol 2018;188:1354-1373. [PMID: 29545196 DOI: 10.1016/j.ajpath.2018.02.007] [Citation(s) in RCA: 50] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/22/2017] [Revised: 02/06/2018] [Accepted: 02/20/2018] [Indexed: 12/20/2022]

Number

Cited by Other Article(s)

Alhendi A, Naser SA. MCT4 inhibition attenuates inflammatory response to Mycobacterium avium paratuberculosis infection and restores intestinal epithelial integrity in vitro. Front Immunol 2025;16:1562100. [PMID: 40297589 PMCID: PMC12034541 DOI: 10.3389/fimmu.2025.1562100] [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: 01/16/2025] [Accepted: 03/24/2025] [Indexed: 04/30/2025] Open

Kim A, Gorman H, Moreau F, McManus M, Dufour A, Chadee K. Human Mucin-2 Mucin-Producing Colonic Goblet-Like Cells Secrete the Chemokine CXCL8 by Activating Multiple Proinflammatory Pathways in Response to Entamoeba histolytica. THE AMERICAN JOURNAL OF PATHOLOGY 2025:S0002-9440(25)00080-X. [PMID: 40122459 DOI: 10.1016/j.ajpath.2025.02.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/09/2024] [Revised: 02/17/2025] [Accepted: 02/27/2025] [Indexed: 03/25/2025]

Di Mattia M, Sallese M, Lopetuso LR. Unfolded protein response: An essential element of intestinal homeostasis and a potential therapeutic target for inflammatory bowel disease. Acta Physiol (Oxf) 2025;241:e14284. [PMID: 39822064 DOI: 10.1111/apha.14284] [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: 06/11/2024] [Revised: 12/23/2024] [Accepted: 01/03/2025] [Indexed: 01/19/2025]

Zhang L, Li J, Wan Q, Bu C, Jin W, Yuan F, Zhou W. Intestinal stem cell-derived extracellular vesicles ameliorate necrotizing enterocolitis injury. Mol Cell Probes 2025;79:101997. [PMID: 39645054 DOI: 10.1016/j.mcp.2024.101997] [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: 08/13/2024] [Revised: 12/05/2024] [Accepted: 12/05/2024] [Indexed: 12/09/2024]

Tozzi M, Fiore A, Travaglione S, Marcon F, Rainaldi G, Germinario EAP, Laterza I, Donati S, Macchia D, Spada M, Leoni O, Quattrini MC, Pietraforte D, Tomasoni S, Torrigiani F, Verin R, Matarrese P, Gambardella L, Spadaro F, Carollo M, Pietrantoni A, Carlini F, Panebianco C, Pazienza V, Colella F, Lucchetti D, Sgambato A, Sistigu A, Moschella F, Guidotti M, Vincentini O, Maroccia Z, Biffoni M, De Angelis R, Bracci L, Fabbri A. E. Coli cytotoxic necrotizing factor-1 promotes colorectal carcinogenesis by causing oxidative stress, DNA damage and intestinal permeability alteration. J Exp Clin Cancer Res 2025;44:29. [PMID: 39876002 PMCID: PMC11776187 DOI: 10.1186/s13046-024-03271-w] [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: 11/23/2024] [Accepted: 12/31/2024] [Indexed: 01/30/2025] Open

Abstract

BACKGROUND

Bacterial toxins are emerging as promising hallmarks of colorectal cancer (CRC) pathogenesis. In particular, Cytotoxic Necrotizing Factor 1 (CNF1) from E. coli deserves special consideration due to the significantly higher prevalence of this toxin gene in CRC patients with respect to healthy subjects, and to the numerous tumor-promoting effects that have been ascribed to the toxin in vitro. Despite this evidence, a definitive causal link between CNF1 and CRC was missing. Here we investigated whether CNF1 plays an active role in CRC onset by analyzing pro-carcinogenic key effects specifically induced by the toxin in vitro and in vivo.

METHODS

Viability assays, confocal microscopy of γH2AX and 53BP1 molecules and cytogenetic analysis were carried out to assess CNF1-induced genotoxicity on non-neoplastic intestinal epithelial cells. Caco-2 monolayers and 3D Caco-2 spheroids were used to evaluate permeability alterations specifically induced by CNF1, either in the presence or in the absence of inflammation. In vivo, an inflammatory bowel disease (IBD) model was exploited to evaluate the carcinogenic potential of CNF1. Immunohistochemistry and immunofluorescence stainings of formalin-fixed paraffin-embedded (FFPE) colon tissue were carried out as well as fecal microbiota composition analysis by 16 S rRNA gene sequencing.

RESULTS

CNF1 induces the release of reactive oxidizing species and chromosomal instability in non-neoplastic intestinal epithelial cells. In addition, CNF1 modifies intestinal permeability by directly altering tight junctions' distribution in 2D Caco-2 monolayers, and by hindering the differentiation of 3D Caco-2 spheroids with an irregular arrangement of these junctions. In vivo, repeated intrarectal administration of CNF1 induces the formation of dysplastic aberrant crypt foci (ACF), and produces the formation of colorectal adenomas in an IBD model. These effects are accompanied by the increased neutrophilic infiltration in colonic tissue, by a mixed pro-inflammatory and anti-inflammatory cytokine milieu, and by the pro-tumoral modulation of the fecal microbiota.

CONCLUSIONS

Taken together, our results support the hypothesis that the CNF1 toxin from E. coli plays an active role in colorectal carcinogenesis. Altogether, these findings not only add new knowledge to the contribution of bacterial toxins to CRC, but also pave the way to the implementation of current screening programs and preventive strategies.

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Affiliation(s)

Michela Tozzi Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy
Alessia Fiore Department of Cardiovascular, Endocrine-Metabolic Diseases and Aging, Istituto Superiore di Sanità, Rome, Italy
Sara Travaglione Department of Cardiovascular, Endocrine-Metabolic Diseases and Aging, Istituto Superiore di Sanità, Rome, Italy
Francesca Marcon Department of Environment and Health, Istituto Superiore di Sanità, Rome, Italy
Gabriella Rainaldi Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy
Elena Angela Pia Germinario Department of Cardiovascular, Endocrine-Metabolic Diseases and Aging, Istituto Superiore di Sanità, Rome, Italy
Ilenia Laterza Department of Cardiovascular, Endocrine-Metabolic Diseases and Aging, Istituto Superiore di Sanità, Rome, Italy
Simona Donati Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy
Daniele Macchia Center of Animal Research and Welfare, Istituto Superiore di Sanità, Rome, Italy
Massimo Spada Center of Animal Research and Welfare, Istituto Superiore di Sanità, Rome, Italy
Omar Leoni Center of Animal Research and Welfare, Istituto Superiore di Sanità, Rome, Italy
Maria Cristina Quattrini Core Facilities, Istituto Superiore di Sanità, Rome, Italy
Donatella Pietraforte Core Facilities, Istituto Superiore di Sanità, Rome, Italy
Sofia Tomasoni Department of Comparative Biomedicine and Food Science, BCA-University of Padua, Legnaro, PD, Italy
Filippo Torrigiani Department of Comparative Biomedicine and Food Science, BCA-University of Padua, Legnaro, PD, Italy
Ranieri Verin Department of Comparative Biomedicine and Food Science, BCA-University of Padua, Legnaro, PD, Italy
Paola Matarrese Center for Gender-Specific Medicine, Istituto Superiore di Sanità, Rome, Italy
Lucrezia Gambardella Center for Gender-Specific Medicine, Istituto Superiore di Sanità, Rome, Italy
Francesca Spadaro Core Facilities, Istituto Superiore di Sanità, Rome, Italy
Maria Carollo Core Facilities, Istituto Superiore di Sanità, Rome, Italy
Agostina Pietrantoni Core Facilities, Istituto Superiore di Sanità, Rome, Italy
Francesca Carlini Department of Cardiovascular, Endocrine-Metabolic Diseases and Aging, Istituto Superiore di Sanità, Rome, Italy
Concetta Panebianco Division of Gastroenterology, Fondazione IRCCS "Casa Sollievo della Sofferenza", San Giovanni Rotondo, FG, Italy
Valerio Pazienza Division of Gastroenterology, Fondazione IRCCS "Casa Sollievo della Sofferenza", San Giovanni Rotondo, FG, Italy
Filomena Colella Multiplex Spatial Profiling Center, Fondazione Policlinico Universitario "A. Gemelli" - IRCCS, Rome, Italy
Donatella Lucchetti Multiplex Spatial Profiling Center, Fondazione Policlinico Universitario "A. Gemelli" - IRCCS, Rome, Italy Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy
Alessandro Sgambato Multiplex Spatial Profiling Center, Fondazione Policlinico Universitario "A. Gemelli" - IRCCS, Rome, Italy Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy
Antonella Sistigu Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy Fondazione Policlinico Universitario "A. Gemelli" - IRCCS, Rome, Italy
Federica Moschella Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy
Marco Guidotti Department of Food Safety, Nutrition and Veterinary Public Health, Istituto Superiore di Sanità, Rome, Italy
Olimpia Vincentini Department of Food Safety, Nutrition and Veterinary Public Health, Istituto Superiore di Sanità, Rome, Italy
Zaira Maroccia Department of Cardiovascular, Endocrine-Metabolic Diseases and Aging, Istituto Superiore di Sanità, Rome, Italy
Mauro Biffoni Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy
Roberta De Angelis Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy
Laura Bracci Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
Alessia Fabbri Department of Cardiovascular, Endocrine-Metabolic Diseases and Aging, Istituto Superiore di Sanità, Rome, Italy

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Wang L, Jin L, Zhang L, Huang X, Li Z, Li Z, Li K, Xu Y, Di S, Cui S, Wang X. Exploring the Link Between Mucin 2 and Weaning Stress-Related Diarrhoea in Piglets. Int J Mol Sci 2025;26:599. [PMID: 39859316 PMCID: PMC11765659 DOI: 10.3390/ijms26020599] [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: 12/07/2024] [Revised: 01/01/2025] [Accepted: 01/10/2025] [Indexed: 01/27/2025] Open

Affiliation(s)

Li Wang College of Animal Science and Technology, Northeast Agricultural University, No. 600 Changjiang Road, Xiangfang District, Harbin 150030, China; (L.W.); (L.J.); (L.Z.); (Z.L.); (Z.L.); (K.L.); (Y.X.); (S.D.)
Long Jin College of Animal Science and Technology, Northeast Agricultural University, No. 600 Changjiang Road, Xiangfang District, Harbin 150030, China; (L.W.); (L.J.); (L.Z.); (Z.L.); (Z.L.); (K.L.); (Y.X.); (S.D.)
Liulian Zhang College of Animal Science and Technology, Northeast Agricultural University, No. 600 Changjiang Road, Xiangfang District, Harbin 150030, China; (L.W.); (L.J.); (L.Z.); (Z.L.); (Z.L.); (K.L.); (Y.X.); (S.D.)
Xuankai Huang Branch of Animal Husbandry and Veterinary, Heilongjiang Academy of Agricultural Sciences, 2 Heyi St., Longsha District, Qiqihaer 161005, China;
Ziyu Li College of Animal Science and Technology, Northeast Agricultural University, No. 600 Changjiang Road, Xiangfang District, Harbin 150030, China; (L.W.); (L.J.); (L.Z.); (Z.L.); (Z.L.); (K.L.); (Y.X.); (S.D.)
Zhimin Li College of Animal Science and Technology, Northeast Agricultural University, No. 600 Changjiang Road, Xiangfang District, Harbin 150030, China; (L.W.); (L.J.); (L.Z.); (Z.L.); (Z.L.); (K.L.); (Y.X.); (S.D.)
Ke Li College of Animal Science and Technology, Northeast Agricultural University, No. 600 Changjiang Road, Xiangfang District, Harbin 150030, China; (L.W.); (L.J.); (L.Z.); (Z.L.); (Z.L.); (K.L.); (Y.X.); (S.D.)
Yuan Xu College of Animal Science and Technology, Northeast Agricultural University, No. 600 Changjiang Road, Xiangfang District, Harbin 150030, China; (L.W.); (L.J.); (L.Z.); (Z.L.); (Z.L.); (K.L.); (Y.X.); (S.D.)
Shengwei Di College of Animal Science and Technology, Northeast Agricultural University, No. 600 Changjiang Road, Xiangfang District, Harbin 150030, China; (L.W.); (L.J.); (L.Z.); (Z.L.); (Z.L.); (K.L.); (Y.X.); (S.D.)
Shiquan Cui College of Animal Science and Technology, Northeast Agricultural University, No. 600 Changjiang Road, Xiangfang District, Harbin 150030, China; (L.W.); (L.J.); (L.Z.); (Z.L.); (Z.L.); (K.L.); (Y.X.); (S.D.)
Xibiao Wang College of Animal Science and Technology, Northeast Agricultural University, No. 600 Changjiang Road, Xiangfang District, Harbin 150030, China; (L.W.); (L.J.); (L.Z.); (Z.L.); (Z.L.); (K.L.); (Y.X.); (S.D.)

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Zhang JY, Li XY, Li DX, Zhang ZH, Hu LQ, Sun CX, Zhang XN, Wu M, Liu LT. Endoplasmic reticulum stress in intestinal microecology: A controller of antineoplastic drug-related cardiovascular toxicity. Biomed Pharmacother 2024;181:117720. [PMID: 39631125 DOI: 10.1016/j.biopha.2024.117720] [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: 08/16/2024] [Revised: 11/20/2024] [Accepted: 11/25/2024] [Indexed: 12/07/2024] Open

Pasam T, Padhy HP, Dandekar MP. Lactobacillus Helveticus Improves Controlled Cortical Impact Injury-Generated Neurological Aberrations by Remodeling of Gut-Brain Axis Mediators. Neurochem Res 2024;50:3. [PMID: 39541016 DOI: 10.1007/s11064-024-04251-4] [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: 06/04/2024] [Revised: 08/15/2024] [Accepted: 10/23/2024] [Indexed: 11/16/2024]

Abstract

Considerable studies augured the potential of gut microbiota-based interventions in brain injury-associated complications. Based on our earlier study results, we envisaged the sex-specific neuroprotective effect of Lactobacillus helveticus by remodeling of gut-brain axis. In this study, we investigated the effect of L. helveticus on neurological complications in a mouse model of controlled cortical impact (CCI). Adult, male and female, C57BL/6 mice underwent CCI surgery and received L. helveticus treatment for six weeks. Sensorimotor function was evaluated via neurological severity score and rotarod test. Long-term effects on anxiety-like behavior and cognition were assessed using the elevated-zero maze (EZM) and novel object recognition test (NORT). Brain perilesional area, blood, colon, and fecal samples were collected post-CCI for molecular biology analysis. CCI-operated mice displayed significant neurological impairments at 1-, 3-, 5-, and 7-days post-injury (dpi) and exhibited altered behavior in EZM and NORT compared to sham-operated mice. However, these behavioral changes were ameliorated in mice receiving L. helveticus. GFAP, Iba-1, TNF-α, and IL-1β expressions and corticotrophin-releasing hormone (CRH) levels were elevated in the perilesional cortex of CCI-operated male/female mice. These elevated biomarkers and decreased BDNF levels in both male/female mice were modified by L. helveticus treatment. Additionally, L. helveticus treatment restored altered short-chain fatty acids (SCFAs) levels in fecal samples and improved intestinal integrity but did not affect decreased plasma levels of progesterone and testosterone in CCI mice. These results indicate that L. helveticus exerts beneficial effects in the CCI mouse model by mitigating inflammation and remodeling of gut microbiota-brain mediators.

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Liu S, Yin J, Wan D, Yin Y. The Role of Iron in Intestinal Mucus: Perspectives from Both the Host and Gut Microbiota. Adv Nutr 2024;15:100307. [PMID: 39341502 PMCID: PMC11533511 DOI: 10.1016/j.advnut.2024.100307] [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: 06/02/2024] [Revised: 09/10/2024] [Accepted: 09/22/2024] [Indexed: 10/01/2024] Open

Zheng M, Xie C, Ye D, Chen Y, Wang Z, Wang L, Xiong F, Zhang S, He Q, Wu H, Wu Z, Zhou H, Li L, Xing J, Miao X. Qingzhuan dark tea polysaccharides-zinc alleviates dextran sodium sulfate-induced ulcerative colitis. JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE 2024;104:7617-7628. [PMID: 38785267 DOI: 10.1002/jsfa.13597] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/25/2023] [Revised: 03/27/2024] [Accepted: 04/29/2024] [Indexed: 05/25/2024]

Affiliation(s)

Min Zheng Xianning Medical College, Hubei University of Science and Technology, Xianning, China Hubei Industrial Technology Research Institute of Intelligent Health, Xianning, China
Chen Xie Xianning Medical College, Hubei University of Science and Technology, Xianning, China Hubei Industrial Technology Research Institute of Intelligent Health, Xianning, China
Dan Ye Xianning Medical College, Hubei University of Science and Technology, Xianning, China Hubei Industrial Technology Research Institute of Intelligent Health, Xianning, China
Yong Chen Xianning Medical College, Hubei University of Science and Technology, Xianning, China Hubei Industrial Technology Research Institute of Intelligent Health, Xianning, China
Ziyao Wang Xianning Medical College, Hubei University of Science and Technology, Xianning, China Hubei Industrial Technology Research Institute of Intelligent Health, Xianning, China
Le Wang Xianning Medical College, Hubei University of Science and Technology, Xianning, China Hubei Industrial Technology Research Institute of Intelligent Health, Xianning, China
Fang Xiong Xianning Medical College, Hubei University of Science and Technology, Xianning, China Hubei Industrial Technology Research Institute of Intelligent Health, Xianning, China
Sheng Zhang Xianning Center for Disease Control and Prevention, Xianning, China
Qiang He Xianning Public Inspection Center of Hubei Province, Xianning, China
Hui Wu Xianning Public Inspection Center of Hubei Province, Xianning, China
Zhinong Wu Xianning Central Hospital, Xianning, China
Hongfu Zhou Xianning Medical College, Hubei University of Science and Technology, Xianning, China Hubei Industrial Technology Research Institute of Intelligent Health, Xianning, China
Ling Li Xianning Medical College, Hubei University of Science and Technology, Xianning, China Hubei Industrial Technology Research Institute of Intelligent Health, Xianning, China
Jun Xing Xianning Medical College, Hubei University of Science and Technology, Xianning, China Hubei Industrial Technology Research Institute of Intelligent Health, Xianning, China
Xiaolei Miao Xianning Medical College, Hubei University of Science and Technology, Xianning, China

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Zheng ZJ, Zhang HY, Hu YL, Li Y, Wu ZH, Li ZP, Chen DR, Luo Y, Zhang XJ, Li C, Wang XY, Xu D, Qiu W, Li HP, Liao XP, Ren H, Sun J. Sleep Deprivation Induces Gut Damage via Ferroptosis. J Pineal Res 2024;76:e12987. [PMID: 38975671 DOI: 10.1111/jpi.12987] [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: 01/11/2024] [Revised: 06/17/2024] [Accepted: 06/25/2024] [Indexed: 07/09/2024]

Affiliation(s)

Zi-Jian Zheng State Key Laboratory for Animal Disease Control and Prevention, South China Agricultural University, Guangzhou, China Guangdong Laboratory for Lingnan Modern Agriculture, National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, South China Agricultural University, Guangzhou, China
Hai-Yi Zhang State Key Laboratory for Animal Disease Control and Prevention, South China Agricultural University, Guangzhou, China Guangdong Laboratory for Lingnan Modern Agriculture, National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, South China Agricultural University, Guangzhou, China
Ya-Lin Hu State Key Laboratory for Animal Disease Control and Prevention, South China Agricultural University, Guangzhou, China Guangdong Laboratory for Lingnan Modern Agriculture, National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, South China Agricultural University, Guangzhou, China
Yan Li State Key Laboratory for Animal Disease Control and Prevention, South China Agricultural University, Guangzhou, China Guangdong Laboratory for Lingnan Modern Agriculture, National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, South China Agricultural University, Guangzhou, China
Zhi-Hong Wu State Key Laboratory for Animal Disease Control and Prevention, South China Agricultural University, Guangzhou, China Guangdong Laboratory for Lingnan Modern Agriculture, National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, South China Agricultural University, Guangzhou, China
Zhi-Peng Li State Key Laboratory for Animal Disease Control and Prevention, South China Agricultural University, Guangzhou, China Guangdong Laboratory for Lingnan Modern Agriculture, National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, South China Agricultural University, Guangzhou, China
Dong-Rui Chen State Key Laboratory for Animal Disease Control and Prevention, South China Agricultural University, Guangzhou, China Guangdong Laboratory for Lingnan Modern Agriculture, National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, South China Agricultural University, Guangzhou, China
Yang Luo State Key Laboratory for Animal Disease Control and Prevention, South China Agricultural University, Guangzhou, China Guangdong Laboratory for Lingnan Modern Agriculture, National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, South China Agricultural University, Guangzhou, China
Xiao-Jing Zhang State Key Laboratory for Animal Disease Control and Prevention, South China Agricultural University, Guangzhou, China Guangdong Laboratory for Lingnan Modern Agriculture, National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, South China Agricultural University, Guangzhou, China
Cang Li State Key Laboratory for Animal Disease Control and Prevention, South China Agricultural University, Guangzhou, China Guangdong Laboratory for Lingnan Modern Agriculture, National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, South China Agricultural University, Guangzhou, China
Xiao-Yu Wang State Key Laboratory for Animal Disease Control and Prevention, South China Agricultural University, Guangzhou, China Guangdong Laboratory for Lingnan Modern Agriculture, National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, South China Agricultural University, Guangzhou, China
Dan Xu State Key Laboratory for Animal Disease Control and Prevention, South China Agricultural University, Guangzhou, China Guangdong Laboratory for Lingnan Modern Agriculture, National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, South China Agricultural University, Guangzhou, China
Wei Qiu Department of Neurology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
Hong-Ping Li Shenzhen Children's Hospital, Shenzhen, China
Xiao-Ping Liao State Key Laboratory for Animal Disease Control and Prevention, South China Agricultural University, Guangzhou, China Guangdong Laboratory for Lingnan Modern Agriculture, National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, South China Agricultural University, Guangzhou, China
Hao Ren State Key Laboratory for Animal Disease Control and Prevention, South China Agricultural University, Guangzhou, China Guangdong Laboratory for Lingnan Modern Agriculture, National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, South China Agricultural University, Guangzhou, China
Jian Sun State Key Laboratory for Animal Disease Control and Prevention, South China Agricultural University, Guangzhou, China Guangdong Laboratory for Lingnan Modern Agriculture, National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, South China Agricultural University, Guangzhou, China

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Lim C, Dandrieux JRS, Ploeg R, Nowell CJ, Firestone SM, Mansfield CS. Evaluation of Ki-67, goblet cell and MUC2 mucin RNA expression in dogs with lymphoplasmacytic and granulomatous colitis. Vet Immunol Immunopathol 2024;271:110740. [PMID: 38537313 DOI: 10.1016/j.vetimm.2024.110740] [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: 11/07/2023] [Revised: 02/20/2024] [Accepted: 02/29/2024] [Indexed: 04/29/2024]

Abstract

Intestinal mucus barrier disruption may occur with chronic inflammatory enteropathies. The lack of studies evaluating mucus health in dogs with chronic colitis arises from inherent challenges with assessment of the intestinal mucus layer. It is therefore unknown if reduced goblet cell (GBC) numbers and/or mucin 2 (MUC2) expression, which are responsible for mucus production and secretion, correlate with inflammation severity in dogs with granulomatous colitis (GC) or lymphocytic-plasmacytic colitis (LPC). It is undetermined if Ki-67 immunoreactivity, which has been evaluated in dogs with small intestinal inflammation, similarly correlates to histologic severity in GC and LPC. Study objectives included comparing Ki-67 immunoreactivity, GBC population and MUC2 expression in dogs with GC, LPC and non-inflamed colon; and exploring the use of ribonucleic acid (RNAscope®) in-situ hybridization (ISH) to evaluate MUC2 expression in canine colon. Formalin-fixed endoscopic colonic biopsies were obtained from 48 dogs over an eight-year period. A blinded pathologist reviewed all biopsies. Dogs were classified into the GC (n=19), LPC (n=19) or no colitis (NC) (n=10) group based on final histopathological diagnosis. Ki-67 immunohistochemistry, Alcian-Blue/PAS staining to highlight GBCs, and RNAscope® ISH using customized canine MUC2-targeted probes were performed. At least five microscopic fields per dog were selected to measure Ki-67 labelling index (KI67%), GBC staining percentage (GBC%) and MUC2 expression (MUC2%) using image analysis software. Spearman's correlation coefficients were used to determine associations between World Small Animal Veterinary Association histologic score (WHS) and measured variables. Linear regression models were used to compare relationships between WHS with KI67%, GBC%, and MUC2%; and between GBC% and MUC2%. Median WHS was highest in dogs with GC. Median KI67% normalised to WHS was highest in the NC group (6.69%; range, 1.70-23.60%). Median GBC% did not correlate with colonic inflammation overall. Median MUC2% normalised to WHS in the NC group (10.02%; range, 3.05-39.09%) was two- and three-fold higher than in the GC and LPC groups respectively. With increased colonic inflammation, despite minimal changes in GBC% overall, MUC2 expression markedly declined in the LPC group (-27.4%; 95%-CI, -49.8, 5.9%) and mildly declined in the GC and NC groups. Granulomatous colitis and LPC likely involve different pathways regulating MUC2 expression. Decreased MUC2 gene expression is observed in dogs with chronic colitis compared to dogs without colonic signs. Changes in MUC2 expression appear influenced by GBC activity rather than quantity in GC and LPC.

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Kassai S, de Vos P. Gastrointestinal barrier function, immunity, and neurocognition: The role of human milk oligosaccharide (hMO) supplementation in infant formula. Compr Rev Food Sci Food Saf 2024;23:e13271. [PMID: 38284595 DOI: 10.1111/1541-4337.13271] [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: 06/30/2023] [Revised: 10/06/2023] [Accepted: 10/27/2023] [Indexed: 01/30/2024]

Bai J, Deng S, Zhang X, Dai Z, Ji Y, Zeng S, Ren F, Yang Y, Wu Z. Cinnamaldehyde alleviates zearalenone-induced LS174T cell apoptosis, barrier dysfunction and mucin reduction through JNK/NF-κB signaling pathway. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2023;263:115276. [PMID: 37499382 DOI: 10.1016/j.ecoenv.2023.115276] [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: 05/08/2023] [Revised: 07/04/2023] [Accepted: 07/17/2023] [Indexed: 07/29/2023]

Inaba R, Vujakovic S, Bergstrom K. The gut mucus network: A dynamic liaison between microbes and the immune system. Semin Immunol 2023;69:101807. [PMID: 37478802 DOI: 10.1016/j.smim.2023.101807] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2022] [Revised: 06/24/2023] [Accepted: 07/08/2023] [Indexed: 07/23/2023]

Chen T, Tang R, Lin J, Kuo W, Yang I, Liang Y, Lin F. The synthesis and evaluation of thiolated alginate as the barrier to block nutrient absorption on small intestine for body-weight control. Bioeng Transl Med 2023;8:e10382. [PMID: 37693067 PMCID: PMC10487312 DOI: 10.1002/btm2.10382] [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: 04/08/2022] [Revised: 07/01/2022] [Accepted: 07/21/2022] [Indexed: 11/12/2022] Open

Gorman H, Moreau F, Dufour A, Chadee K. IgGFc-binding protein and MUC2 mucin produced by colonic goblet-like cells spatially interact non-covalently and regulate wound healing. Front Immunol 2023;14:1211336. [PMID: 37359538 PMCID: PMC10285406 DOI: 10.3389/fimmu.2023.1211336] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2023] [Accepted: 05/30/2023] [Indexed: 06/28/2023] Open

Liu Y, Yu Z, Zhu L, Ma S, Luo Y, Liang H, Liu Q, Chen J, Guli S, Chen X. Orchestration of MUC2 - The key regulatory target of gut barrier and homeostasis: A review. Int J Biol Macromol 2023;236:123862. [PMID: 36870625 DOI: 10.1016/j.ijbiomac.2023.123862] [Citation(s) in RCA: 40] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2022] [Revised: 02/22/2023] [Accepted: 02/24/2023] [Indexed: 03/06/2023]

Affiliation(s)

Yaxin Liu Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin 300052, China; Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin 300052, China
Zihan Yu Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin 300052, China; Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin 300052, China
Lanping Zhu Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin 300052, China; Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin 300052, China
Shuang Ma Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin 300052, China; Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin 300052, China
Yang Luo Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin 300052, China; Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin 300052, China
Huixi Liang Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin 300052, China; Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin 300052, China
Qinlingfei Liu Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin 300052, China; Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin 300052, China
Jihua Chen Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin 300052, China; Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin 300052, China
Sitan Guli Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin 300052, China; Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin 300052, China
Xin Chen Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin 300052, China; Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin 300052, China.

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Hussein EM, Muhammad MAA, Hussein AM, Elzagawy SM, Zaki WM, Temsah AG, Badr MS, Alabbassy MM. Levels of Genetic Variants Among Symptomatic Blastocystis Subtypes and their Relationship to Mucosal Immune Surveillance in the Precancerous Colons of Experimentally Infected Rats. Acta Parasitol 2023;68:70-83. [PMID: 36380160 PMCID: PMC10011339 DOI: 10.1007/s11686-022-00628-z] [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: 03/25/2022] [Accepted: 10/03/2022] [Indexed: 11/16/2022]

Abstract

PURPOSE

The relationship between the genetic diversity of Blastocystis and immune surveillance in precancerous colons with blastocystosis is still under investigation. This study aimed to identify the genetic Blastocystis variants among 54 symptomatic human isolates and their relationship to mucosal immune surveillance in the precancerous polyps of experimentally infected rats.

METHODS

Polymerase chain reaction and high-resolution melting (PCR/HRM) curves discriminated human symptomatic Blastocystis isolates into subtypes (STs)/intrasubtypes, which were orally administered to rats to induce experimental infection. Then, the mucosal immune responses of the infected colons were evaluated in relation to polyp formation through immunostaining to identify mucus MUC2 and determine mucosal immune cell (goblet, lymphocyte and mast) counts, secretory IgA levels and parasitic intestinal invasion.

RESULTS

ST1, ST3, and ST4 were found in 18.5% (10/54), 54.7% (29/54), and 27.8% (15/54) of the samples, respectively. Then, the HRM curve discriminated ST3 into the wild, mutant, and heterozygous [17/54 (31.5%), 5/54 (9.3%), and 7/54 (12.9%)] intrasubtypes. ST1 and ST4 had no genetic variations. Precancerous polyps were detected in the colons of 40.5% of the infected rats. ST1 constituted 14.7% of these cases, while the wild, mutant, and heterozygous intrasubtypes of ST3 showed polyps in 12.9%, 5.5%, and 5.5% of cases, respectively. Only 1.9% of the polyps were related to ST4. MUC2 showed weak immunostaining in 44.5% of the infected colons, and 38.9% were polyp inducers. Low goblet cell numbers and high interepithelial lymphocyte counts were significantly associated with polyp formation, particularly with ST1 and wild ST3. Among the polyp inducers, high numbers of mast cells were detected in wild ST3 and ST4, while a low number was found with heterozygous ST3. The level of secretory IgA was low in polyp-inducing STs. Most of the results were statistically significant.

CONCLUSION

Immunosurveillance showed a potential relationship between ST1 and the ST3 intrasubtypes and precancerous polyps. This relationship may provide insight into the prevention and/or development of new immunotherapeutic strategies to combat colorectal cancer.

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Chen H, Sun HM, Wu B, Sun TY, Han LZ, Wang G, Shang YF, Yang S, Zhou DS. Artesunate delays the dysfunction of age-related intestinal epithelial barrier by mitigating endoplasmic reticulum stress/unfolded protein response. Mech Ageing Dev 2023;210:111760. [PMID: 36476344 DOI: 10.1016/j.mad.2022.111760] [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: 08/19/2022] [Revised: 12/01/2022] [Accepted: 12/02/2022] [Indexed: 12/12/2022]

Kiparissi F, Dastamani A, Palm L, Azabdaftari A, Campos L, Gaynor E, Grünewald S, Uhlig HH, Kleta R, Böckenhauer D, Jones KDJ. Phosphomannomutase 2 (PMM2) variants leading to hyperinsulinism-polycystic kidney disease are associated with early-onset inflammatory bowel disease and gastric antral foveolar hyperplasia. Hum Genet 2023;142:697-704. [PMID: 36773065 PMCID: PMC10181953 DOI: 10.1007/s00439-023-02523-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2022] [Accepted: 01/19/2023] [Indexed: 02/12/2023]

Song S, Tu D, Meng C, Liu J, Wilson B, Wang Q, Shih YYI, Gao HM, Hong JS. Dysfunction of the noradrenergic system drives inflammation, α-synucleinopathy, and neuronal loss in mouse colon. Front Immunol 2023;14:1083513. [PMID: 36845109 PMCID: PMC9950510 DOI: 10.3389/fimmu.2023.1083513] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2022] [Accepted: 02/01/2023] [Indexed: 02/12/2023] Open

Abstract

Clinical and pathological evidence revealed that α-synuclein (α-syn) pathology seen in PD patients starts in the gut and spreads via anatomically connected structures from the gut to the brain. Our previous study demonstrated that depletion of central norepinephrine (NE) disrupted brain immune homeostasis, producing a spatiotemporal order of neurodegeneration in the mouse brain. The purpose of this study was 1) to determine the role of peripheral noradrenergic system in the maintenance of gut immune homeostasis and in the pathogenesis of PD and 2) to investigate whether NE-depletion induced PD-like α-syn pathological changes starts from the gut. For these purposes, we investigated time-dependent changes of α-synucleinopathy and neuronal loss in the gut following a single injection of DSP-4 (a selective noradrenergic neurotoxin) to A53T-SNCA (human mutant α-syn) over-expression mice. We found DPS-4 significantly reduced the tissue level of NE and increased immune activities in gut, characterized by increased number of phagocytes and proinflammatory gene expression. Furthermore, a rapid-onset of α-syn pathology was observed in enteric neurons after 2 weeks and delayed dopaminergic neurodegeneration in the substantia nigra was detected after 3-5 months, associated with the appearance of constipation and impaired motor function, respectively. The increased α-syn pathology was only observed in large, but not in the small, intestine, which is similar to what was observed in PD patients. Mechanistic studies reveal that DSP-4-elicited upregulation of NADPH oxidase (NOX2) initially occurred only in immune cells during the acute intestinal inflammation stage, and then spread to enteric neurons and mucosal epithelial cells during the chronic inflammation stage. The upregulation of neuronal NOX2 correlated well with the extent of α-syn aggregation and subsequent enteric neuronal loss, suggesting that NOX2-generated reactive oxygen species play a key role in α-synucleinopathy. Moreover, inhibiting NOX2 by diphenyleneiodonium or restoring NE function by salmeterol (a β2-receptor agonist) significantly attenuated colon inflammation, α-syn aggregation/propagation, and enteric neurodegeneration in the colon and ameliorated subsequent behavioral deficits. Taken together, our model of PD shows a progressive pattern of pathological changes from the gut to the brain and suggests a potential role of the noradrenergic dysfunction in the pathogenesis of PD.

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Affiliation(s)

Sheng Song Neuropharmacology Section, Neurobiology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, United States Biomedical Research Imaging Center, University of North Caroline at Chapel Hill, Chapel Hill, NC, United States
Dezhen Tu Neuropharmacology Section, Neurobiology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, United States Ministry of Education (MOE) Key Laboratory of Model Animal for Disease Study, Institute for Brain Sciences, Jiangsu Key Laboratory of Molecular Medicine, Model Animal Research Center, School of medicine, Nanjing University, Nanjing, China
Chengbo Meng In Vivo Neurobiology Group, Neurobiology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, United States
Jie Liu Neuropharmacology Section, Neurobiology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, United States
Belinda Wilson Neuropharmacology Section, Neurobiology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, United States
Qingshan Wang National-Local Joint Engineering Research Center for Drug-Research and Development (R & D) of Neurodegenerative Diseases, Dalian Medical University, Dalian, China
Yen-Yu Ian Shih Biomedical Research Imaging Center, University of North Caroline at Chapel Hill, Chapel Hill, NC, United States
Hui-Ming Gao Ministry of Education (MOE) Key Laboratory of Model Animal for Disease Study, Institute for Brain Sciences, Jiangsu Key Laboratory of Molecular Medicine, Model Animal Research Center, School of medicine, Nanjing University, Nanjing, China
Jau-Shyong Hong Neuropharmacology Section, Neurobiology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, United States

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Fernández-Lainez C, Aan de Stegge M, Silva-Lagos LA, López-Velázquez G, de Vos P. β(2 → 1)-β(2 → 6) branched graminan-type fructans and β(2 → 1) linear fructans impact mucus-related and endoplasmic reticulum stress-related genes in goblet cells and attenuate inflammatory responses in a fructan dependent fashion. Food Funct 2023;14:1338-1348. [PMID: 36656019 DOI: 10.1039/d2fo02710k] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]

Sun B, Huang Y, Castro LFC, Yang S, Huang S, Jin W, Zhou H, Ijiri S, Luo Y, Gao J, Cao X. The chromosome-level genome and key genes associated with mud-dwelling behavior and adaptations of hypoxia and noxious environments in loach (Misgurnus anguillicaudatus). BMC Biol 2023;21:18. [PMID: 36726103 PMCID: PMC9893644 DOI: 10.1186/s12915-023-01517-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2022] [Accepted: 01/18/2023] [Indexed: 02/03/2023] Open

Affiliation(s)

Bing Sun College of Fisheries, Engineering Research Center of Green development for Conventional Aquatic Biological Industry in the Yangtze River Economic Belt, Ministry of Education, Huazhong Agricultural University, Postal address: No.1 Shizishan Stress, Hongshan District, Wuhan, 430070, Hubei Province, China
Yuwei Huang College of Fisheries, Engineering Research Center of Green development for Conventional Aquatic Biological Industry in the Yangtze River Economic Belt, Ministry of Education, Huazhong Agricultural University, Postal address: No.1 Shizishan Stress, Hongshan District, Wuhan, 430070, Hubei Province, China
L Filipe C Castro Interdisciplinary Centre of Marine and Environmental Research of the University of Porto, 4450-208, Matosinhos, Portugal Department of Biology, University of Porto, 4450-208, Porto, Portugal
Su Yang College of Fisheries, Engineering Research Center of Green development for Conventional Aquatic Biological Industry in the Yangtze River Economic Belt, Ministry of Education, Huazhong Agricultural University, Postal address: No.1 Shizishan Stress, Hongshan District, Wuhan, 430070, Hubei Province, China
Songqian Huang Department of Aquatic Bioscience, Graduate School of Agricultural and Life Sciences, the University of Tokyo, Bunkyo, Tokyo, 113-8657, Japan
Wu Jin Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxi, 214081, Jiangsu, China
He Zhou College of Fisheries and Life Science, Dalian Ocean University, Dalian, 116023, China
Shigeho Ijiri Division of Marine Life Sciences, Graduate School of Fisheries Sciences, Hokkaido University, Hakodate, Hokkaido, 041-8611, Japan
Yi Luo College of Fisheries, Engineering Research Center of Green development for Conventional Aquatic Biological Industry in the Yangtze River Economic Belt, Ministry of Education, Huazhong Agricultural University, Postal address: No.1 Shizishan Stress, Hongshan District, Wuhan, 430070, Hubei Province, China
Jian Gao College of Fisheries, Engineering Research Center of Green development for Conventional Aquatic Biological Industry in the Yangtze River Economic Belt, Ministry of Education, Huazhong Agricultural University, Postal address: No.1 Shizishan Stress, Hongshan District, Wuhan, 430070, Hubei Province, China.
Xiaojuan Cao College of Fisheries, Engineering Research Center of Green development for Conventional Aquatic Biological Industry in the Yangtze River Economic Belt, Ministry of Education, Huazhong Agricultural University, Postal address: No.1 Shizishan Stress, Hongshan District, Wuhan, 430070, Hubei Province, China.

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ERdj5 protects goblet cells from endoplasmic reticulum stress-mediated apoptosis under inflammatory conditions. Exp Mol Med 2023;55:401-412. [PMID: 36759578 PMCID: PMC9981579 DOI: 10.1038/s12276-023-00945-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2022] [Revised: 11/21/2022] [Accepted: 12/06/2022] [Indexed: 02/11/2023] Open

Cari L, Rosati L, Leoncini G, Lusenti E, Gentili M, Nocentini G, Riccardi C, Migliorati G, Ronchetti S. Association of GILZ with MUC2, TLR2, and TLR4 in Inflammatory Bowel Disease. Int J Mol Sci 2023;24:ijms24032235. [PMID: 36768553 PMCID: PMC9917296 DOI: 10.3390/ijms24032235] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2022] [Revised: 01/13/2023] [Accepted: 01/19/2023] [Indexed: 01/26/2023] Open

Tang Y, Zhou X, Cao T, Chen E, Li Y, Lei W, Hu Y, He B, Liu S. Endoplasmic Reticulum Stress and Oxidative Stress in Inflammatory Diseases. DNA Cell Biol 2022;41:924-934. [PMID: 36356165 DOI: 10.1089/dna.2022.0353] [Citation(s) in RCA: 33] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open

Affiliation(s)

Yun Tang Department of Clinical Laboratory Medicine, Institution of Microbiology and Infectious Diseases, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China
Xiangping Zhou Department of Clinical Laboratory Medicine, Institution of Microbiology and Infectious Diseases, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China
Ting Cao Department of Clinical Laboratory Medicine, Institution of Microbiology and Infectious Diseases, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China
En Chen Department of Clinical Laboratory Medicine, Institution of Microbiology and Infectious Diseases, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China
Yumeng Li Department of Clinical Laboratory Medicine, Institution of Microbiology and Infectious Diseases, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China
Wenbo Lei Department of Clinical Laboratory Medicine, Institution of Microbiology and Infectious Diseases, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China
Yibao Hu Department of Clinical Laboratory Medicine, Institution of Microbiology and Infectious Diseases, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China
Bisha He Department of Clinical Laboratory Medicine, Institution of Microbiology and Infectious Diseases, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China
Shuangquan Liu Department of Clinical Laboratory Medicine, Institution of Microbiology and Infectious Diseases, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China

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Tao Y, Qiao S, Lv C, Yun X, Yue M, Fang Y, Wei Z, Dai Y, Xia Y. Phytoestrogen arctigenin preserves the mucus barrier in inflammatory bowel diseases by inhibiting goblet cell apoptosis via the ERβ / TRIM21 / PHB1 pathway. Phytother Res 2022;36:3248-3264. [DOI: 10.1002/ptr.7495] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2022] [Revised: 04/26/2022] [Accepted: 04/30/2022] [Indexed: 01/17/2023]

Livzan MA, Bicbavova GR, Romanyuk AE. Ulcerative colitis: focus on colonic mucosal resistance. BULLETIN OF SIBERIAN MEDICINE 2022;21:121-132. [DOI: 10.20538/1682-0363-2022-1-121-132] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/17/2024]

Liang X, Xie J, Liu H, Zhao R, Zhang W, Wang H, Pan H, Zhou Y, Han W. STIM1 Deficiency In Intestinal Epithelium Attenuates Colonic Inflammation and Tumorigenesis by Reducing ER Stress of Goblet Cells. Cell Mol Gastroenterol Hepatol 2022;14:193-217. [PMID: 35367664 PMCID: PMC9130113 DOI: 10.1016/j.jcmgh.2022.03.007] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2021] [Revised: 03/23/2022] [Accepted: 03/24/2022] [Indexed: 12/25/2022]

Abstract

BACKGROUND & AIMS

As an indispensable component of store-operated Ca²⁺ entry, stromal interaction molecule 1 (STIM1) is known to promote colorectal cancer and T-cell-mediated inflammatory diseases. However, whether the intestinal mucosal STIM1 is involved in inflammatory bowel diseases (IBDs) is unclear. This study aimed to investigate the role of intestinal epithelial STIM1 in IBD.

METHODS

Inflammatory and matched normal intestinal tissues were collected from IBD patients to investigate the expression of STIM1. Intestinal epithelium-specific STIM1 conditional knockout mice (STIM1^ΔIEC) were generated and induced to develop colitis and colitis-associated colorectal cancer. The mucosal barrier, including the epithelial barrier and mucus barrier, was analyzed. The mechanisms by which STIM1 regulate goblet cell endoplasmic reticulum stress and apoptosis were assessed.

RESULTS

STIM1 could regulate intestinal epithelial homeostasis. STIM1 was augmented in the inflammatory intestinal tissues of IBD patients. In dextran sodium sulfate-induced colitis, STIM1 deficiency in intestinal epithelium reduced the loss of goblet cells through alleviating endoplasmic reticulum stress induced by disturbed Ca²⁺ homeostasis, resulting in the maintenance of the integrated mucus layer. These effects prevented commensal bacteria from contacting and stimulating the intestinal epithelium of STIM1^ΔIEC mice and thereby rendered STIM1^ΔIEC mice less susceptible to colitis and colitis-associated colorectal cancer. In addition, microbial diversity in dextran sodium sulfate-treated STIM1^ΔIEC mice slightly shifted to an advantageous bacteria, which further protected the intestinal epithelium.

CONCLUSIONS

Our results establish STIM1 as a crucial regulator for the maintenance of the intestinal barrier during colitis and provide a potential target for IBD treatment.

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Wanner N, Barnhart J, Apostolakis N, Zlojutro V, Asosingh K. Using the Autofluorescence Finder on the Sony ID7000^TM Spectral Cell Analyzer to Identify and Unmix Multiple Highly Autofluorescent Murine Lung Populations. Front Bioeng Biotechnol 2022;10:827987. [PMID: 35372303 PMCID: PMC8965042 DOI: 10.3389/fbioe.2022.827987] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Accepted: 02/25/2022] [Indexed: 11/13/2022] Open

Al Saedi A, Sharma S, Bani Hassan E, Chen L, Ghasem-Zadeh A, Hassanzadeganroudsari M, Gooi JH, Stavely R, Eri R, Miao D, Nurgali K, Duque G. Characterization of Skeletal Phenotype and Associated Mechanisms With Chronic Intestinal Inflammation in the Winnie Mouse Model of Spontaneous Chronic Colitis. Inflamm Bowel Dis 2022;28:259-272. [PMID: 34347076 DOI: 10.1093/ibd/izab174] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2021] [Indexed: 12/09/2022]

Abstract

BACKGROUND

Osteoporosis is a common extraintestinal manifestation of inflammatory bowel disease (IBD). However, studies have been scarce, mainly because of the lack of an appropriate animal model of colitis-associated bone loss. In this study, we aimed to decipher skeletal manifestations in the Winnie mouse model of spontaneous chronic colitis, which carries a MUC2 gene mutation and closely replicates ulcerative colitis. In our study, Winnie mice, prior to the colitis onset at 6 weeks old and progression at 14 and 24 weeks old, were compared with age-matched C57BL/6 controls. We studied several possible mechanisms involved in colitis-associated bone loss.

METHODS

We assessed for bone quality (eg, microcomputed tomography [micro-CT], static and dynamic histomorphometry, 3-point bending, and ex vivo bone marrow analysis) and associated mechanisms (eg, electrochemical recordings for gut-derived serotonin levels, real-time polymerase chain reaction [qRT-PCR], double immunofluorescence microscopy, intestinal inflammation levels by lipocalin-2 assay, serum levels of calcium, phosphorus, and vitamin D) from Winnie (6-24 weeks) and age-matched C57BL6 mice.

RESULTS

Deterioration in trabecular and cortical bone microarchitecture, reductions in bone formation, mineral apposition rate, bone volume/total volume, osteoid volume/bone surface, and bone strength were observed in Winnie mice compared with controls. Decreased osteoblast and increased osteoclast numbers were prominent in Winnie mice compared with controls. Upregulation of 5-HTR1B gene and increased association of FOXO1 with ATF4 complex were identified as associated mechanisms concomitant to overt inflammation and high levels of gut-derived serotonin in 14-week and 24-week Winnie mice.

CONCLUSIONS

Skeletal phenotype of the Winnie mouse model of spontaneous chronic colitis closely represents manifestations of IBD-associated osteoporosis/osteopenia. The onset and progression of intestinal inflammation are associated with increased gut-derived serotonin level, increased bone resorption, and decreased bone formation.

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Affiliation(s)

Ahmed Al Saedi Department of Medicine-Western Health, The University of Melbourne, Melbourne, VIC, Australia Australian Institute for Musculoskeletal Science (AIMSS), Department of Medicine-Western Health, Melbourne, VIC, Australia
Shilpa Sharma Department of Medicine-Western Health, The University of Melbourne, Melbourne, VIC, Australia Australian Institute for Musculoskeletal Science (AIMSS), Department of Medicine-Western Health, Melbourne, VIC, Australia
Ebrahim Bani Hassan Department of Medicine-Western Health, The University of Melbourne, Melbourne, VIC, Australia Australian Institute for Musculoskeletal Science (AIMSS), Department of Medicine-Western Health, Melbourne, VIC, Australia
Lulu Chen Department of Anatomy, Histology and Embryology, Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China
Ali Ghasem-Zadeh Australian Institute for Musculoskeletal Science (AIMSS), Department of Medicine-Western Health, Melbourne, VIC, Australia Departments of Medicine and Endocrinology, Austin Health, The University of Melbourne, Melbourne, VIC, Australia
Majid Hassanzadeganroudsari Institute for Health and Sport, Victoria University, Melbourne, VIC, Australia
Jonathan H Gooi St. Vincent's Institute of Medical Research, Melbourne, VIC, Australia Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Melbourne, VIC, Australia
Rhian Stavely Institute for Health and Sport, Victoria University, Melbourne, VIC, Australia Department of Pediatric Surgery, Pediatric Surgery Research Laboratories, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Rajaraman Eri School of Health Sciences, University of Tasmania, Launceston, TAS, Australia
Dengshun Miao Department of Anatomy, Histology and Embryology, Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China Calcium Research Laboratory, McGill University Health Centre and Department of Medicine, McGill University, Montreal, QC, Canada
Kulmira Nurgali Department of Medicine-Western Health, The University of Melbourne, Melbourne, VIC, Australia Australian Institute for Musculoskeletal Science (AIMSS), Department of Medicine-Western Health, Melbourne, VIC, Australia Institute for Health and Sport, Victoria University, Melbourne, VIC, Australia
Gustavo Duque Department of Medicine-Western Health, The University of Melbourne, Melbourne, VIC, Australia Australian Institute for Musculoskeletal Science (AIMSS), Department of Medicine-Western Health, Melbourne, VIC, Australia

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Zhu L, Miao B, Dymerska D, Kuswik M, Bueno-Martínez E, Sanoguera-Miralles L, Velasco EA, Paramasivam N, Schlesner M, Kumar A, Yuan Y, Lubinski J, Bandapalli OR, Hemminki K, Försti A. Germline Variants of CYBA and TRPM4 Predispose to Familial Colorectal Cancer. Cancers (Basel) 2022;14:cancers14030670. [PMID: 35158942 PMCID: PMC8833488 DOI: 10.3390/cancers14030670] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Revised: 01/17/2022] [Accepted: 01/26/2022] [Indexed: 02/07/2023] Open

Abstract

Simple Summary

Whole-genome sequencing and bioinformatics analysis on unique colorectal cancer families revealed two attractive candidate predisposition genes, CYBA and TRPM4, each with a loss-of-function variant. Supported by our functional studies, we suggest that the two gene defects mechanistically involve intestinal barrier integrity through reactive oxygen species and mucus biology, which converges in chronic bowel inflammation, a known risk factor for colorectal cancer.

Abstract

Familial colorectal cancer (CRC) is only partially explained by known germline predisposing genes. We performed whole-genome sequencing in 15 Polish families of many affected individuals, without mutations in known CRC predisposing genes. We focused on loss-of-function variants and functionally characterized them. We identified a frameshift variant in the CYBA gene (c.246delC) in one family and a splice site variant in the TRPM4 gene (c.25–1 G > T) in another family. While both variants were absent or extremely rare in gene variant databases, we identified four additional Polish familial CRC cases and two healthy elderly individuals with the CYBA variant (odds ratio 2.46, 95% confidence interval 0.48–12.69). Both variants led to a premature stop codon and to a truncated protein. Functional characterization of the variants showed that knockdown of CYBA or TRPM4 depressed generation of reactive oxygen species (ROS) in LS174T and HT-29 cell lines. Knockdown of TRPM4 resulted in decreased MUC2 protein production. CYBA encodes a component in the NADPH oxidase system which generates ROS and controls, e.g., bacterial colonization in the gut. Germline CYBA variants are associated with early onset inflammatory bowel disease, supported with experimental evidence on loss of intestinal mucus barrier function due to ROS deficiency. TRPM4 encodes a calcium-activated ion channel, which, in a human colonic cancer cell line, controls calcium-mediated secretion of MUC2, a major component of intestinal mucus barrier. We suggest that the gene defects in CYBA and TRPM4 mechanistically involve intestinal barrier integrity through ROS and mucus biology, which converges in chronic bowel inflammation.

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Affiliation(s)

Lizhen Zhu Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 580, D-69120 Heidelberg, Germany; (L.Z.); (B.M.); (A.K.); (A.F.) Department of Medical Oncology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, China;
Beiping Miao Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 580, D-69120 Heidelberg, Germany; (L.Z.); (B.M.); (A.K.); (A.F.) Hopp Children’s Cancer Center (KiTZ), D-69120 Heidelberg, Germany Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), D-69120 Heidelberg, Germany
Dagmara Dymerska Department of Genetics and Pathology, Hereditary Cancer Center, Pomeranian Medical University, Unii Lubelskiej 1, 71-252 Szczecin, Poland; (D.D.); (M.K.); (J.L.)
Magdalena Kuswik Department of Genetics and Pathology, Hereditary Cancer Center, Pomeranian Medical University, Unii Lubelskiej 1, 71-252 Szczecin, Poland; (D.D.); (M.K.); (J.L.)
Elena Bueno-Martínez Splicing and Genetic Susceptibility to Cancer, Instituto de Biología y Genética Molecular (CSIC-UVa), 47003 Valladolid, Spain; (E.B.-M.); (L.S.-M.); (E.A.V.)
Lara Sanoguera-Miralles Splicing and Genetic Susceptibility to Cancer, Instituto de Biología y Genética Molecular (CSIC-UVa), 47003 Valladolid, Spain; (E.B.-M.); (L.S.-M.); (E.A.V.)
Eladio A. Velasco Splicing and Genetic Susceptibility to Cancer, Instituto de Biología y Genética Molecular (CSIC-UVa), 47003 Valladolid, Spain; (E.B.-M.); (L.S.-M.); (E.A.V.)
Nagarajan Paramasivam Computational Oncology, Molecular Diagnostics Program, National Center for Tumor Diseases (NCT), D-69120 Heidelberg, Germany;
Matthias Schlesner Bioinformatics and Omics Data Analytics, German Cancer Research Center (DKFZ), D-69120 Heidelberg, Germany;
Abhishek Kumar Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 580, D-69120 Heidelberg, Germany; (L.Z.); (B.M.); (A.K.); (A.F.) Institute of Bioinformatics, International Technology Park, Bengaluru 560066, India Manipal Academy of Higher Education (MAHE), Manipal 576104, India
Ying Yuan Department of Medical Oncology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, China;
Jan Lubinski Department of Genetics and Pathology, Hereditary Cancer Center, Pomeranian Medical University, Unii Lubelskiej 1, 71-252 Szczecin, Poland; (D.D.); (M.K.); (J.L.)
Obul Reddy Bandapalli Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 580, D-69120 Heidelberg, Germany; (L.Z.); (B.M.); (A.K.); (A.F.) Hopp Children’s Cancer Center (KiTZ), D-69120 Heidelberg, Germany Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), D-69120 Heidelberg, Germany Medical Faculty Heidelberg, Heidelberg University, D-69120 Heidelberg, Germany Correspondence: (O.R.B.); (K.H.)
Kari Hemminki Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 580, D-69120 Heidelberg, Germany; (L.Z.); (B.M.); (A.K.); (A.F.) Faculty of Medicine and Biomedical Center in Pilsen, Charles University in Prague, 30605 Pilsen, Czech Republic Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), D-69120 Heidelberg, Germany Correspondence: (O.R.B.); (K.H.)
Asta Försti Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 580, D-69120 Heidelberg, Germany; (L.Z.); (B.M.); (A.K.); (A.F.) Hopp Children’s Cancer Center (KiTZ), D-69120 Heidelberg, Germany Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), D-69120 Heidelberg, Germany

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A Novel Pseudoalteromonas xiamenensis Marine Isolate as a Potential Probiotic: Anti-Inflammatory and Innate Immune Modulatory Effects against Thermal and Pathogenic Stresses. Mar Drugs 2021;19:md19120707. [PMID: 34940706 PMCID: PMC8707914 DOI: 10.3390/md19120707] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2021] [Revised: 12/11/2021] [Accepted: 12/12/2021] [Indexed: 11/16/2022] Open

MUC2 and related bacterial factors: Therapeutic targets for ulcerative colitis. EBioMedicine 2021;74:103751. [PMID: 34902790 PMCID: PMC8671112 DOI: 10.1016/j.ebiom.2021.103751] [Citation(s) in RCA: 124] [Impact Index Per Article: 31.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2021] [Revised: 11/21/2021] [Accepted: 11/30/2021] [Indexed: 12/26/2022] Open

Parrish A, Boudaud M, Kuehn A, Ollert M, Desai MS. Intestinal mucus barrier: a missing piece of the puzzle in food allergy. Trends Mol Med 2021;28:36-50. [PMID: 34810087 DOI: 10.1016/j.molmed.2021.10.004] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2021] [Revised: 10/22/2021] [Accepted: 10/22/2021] [Indexed: 12/13/2022]

Tiwari S, Begum S, Moreau F, Gorman H, Chadee K. Autophagy is required during high MUC2 mucin biosynthesis in colonic goblet cells to contend metabolic stress. Am J Physiol Gastrointest Liver Physiol 2021;321:G489-G499. [PMID: 34494458 DOI: 10.1152/ajpgi.00221.2021] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2021] [Accepted: 09/02/2021] [Indexed: 01/31/2023]

Abstract

Goblet cells are specialized for the production and secretion of MUC2 glycoproteins that forms a thick layer covering the mucosal epithelium as a protective barrier against noxious substances and invading microbes. High MUC2 mucin biosynthesis induces endoplasmic reticulum (ER) stress and apoptosis in goblet cells during inflammatory and infectious diseases. Autophagy is an intracellular degradation process required for maintenance of intestinal homeostasis. In this study, we hypothesized that autophagy was triggered during high MUC2 mucin biosynthesis from colonic goblet cells to cope with metabolic stress. To interrogate this, we analyzed the autophagy process in high MUC2-producing human HT29-H and a clone HT29-L silenced for MUC2 expression by lentivirus-mediated shRNA, and WT and CRISPR/Cas9 MUC2 KO LS174T cells. Autophagy was constitutively increased in high MUC2-producing cells characterized by elevated pULK1S555 expression and increased numbers of autophagosomes as compared with MUC2 silenced or gene edited cells. Similarly, colonoids from Muc2+/+ but not Muc2-/- littermates differentiated into goblet cells showed increased autophagy. IL-22 treatment corrected misfolded MUC2 protein and alleviated the autophagy process in LS174T cells. This study highlights that autophagy plays an essential role in goblet cells to survive during high mucin biosynthesis by regulating cellular homeostasis.NEW & NOTEWORTHY It is unclear how colonic goblet cells survive by producing high output MUC2 mucin that triggers endoplasmic stress by misfolded MUC2 proteins. To cope with metabolic stress, we interrogated if autophagy played an essential role in regulating cellular homeostasis. Indeed, high MUC2 mucin biosynthesis dysregulated autophagy processes that was regulated by IL-22 to maintain gut barrier innate host defenses.

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Chidambaram SB, Essa MM, Rathipriya AG, Bishir M, Ray B, Mahalakshmi AM, Tousif AH, Sakharkar MK, Kashyap RS, Friedland RP, Monaghan TM. Gut dysbiosis, defective autophagy and altered immune responses in neurodegenerative diseases: Tales of a vicious cycle. Pharmacol Ther 2021;231:107988. [PMID: 34536490 DOI: 10.1016/j.pharmthera.2021.107988] [Citation(s) in RCA: 101] [Impact Index Per Article: 25.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2021] [Revised: 08/16/2021] [Accepted: 08/25/2021] [Indexed: 02/08/2023]

Abstract

The human microbiota comprises trillions of symbiotic microorganisms and is involved in regulating gastrointestinal (GI), immune, nervous system and metabolic homeostasis. Recent observations suggest a bidirectional communication between the gut microbiota and the brain via immune, circulatory and neural pathways, termed the Gut-Brain Axis (GBA). Alterations in gut microbiota composition, such as seen with an increased number of pathobionts and a decreased number of symbionts, termed gut dysbiosis or microbial intestinal dysbiosis, plays a prominent role in the pathogenesis of central nervous system (CNS)-related disorders. Clinical reports confirm that GI symptoms often precede neurological symptoms several years before the development of neurodegenerative diseases (NDDs). Pathologically, gut dysbiosis disrupts the integrity of the intestinal barrier leading to ingress of pathobionts and toxic metabolites into the systemic circulation causing GBA dysregulation. Subsequently, chronic neuroinflammation via dysregulated immune activation triggers the accumulation of neurotoxic misfolded proteins in and around CNS cells resulting in neuronal death. Emerging evidence links gut dysbiosis to the aggravation and/or spread of proteinopathies from the peripheral nervous system to the CNS and defective autophagy-mediated proteinopathies. This review summarizes the current understanding of the role of gut microbiota in NDDs, and highlights a vicious cycle of gut dysbiosis, immune-mediated chronic neuroinflammation, impaired autophagy and proteinopathies, which contributes to the development of neurodegeneration in Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis, amyotrophic lateral sclerosis and frontotemporal lobar degeneration. We also discuss novel therapeutic strategies targeting the modulation of gut dysbiosis through prebiotics, probiotics, synbiotics or dietary interventions, and faecal microbial transplantation (FMT) in the management of NDDs.

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Affiliation(s)

Saravana Babu Chidambaram Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Mysuru 570015, KA, India; Centre for Experimental Pharmacology and Toxicology (CPT), JSS Academy of Higher Education & Research, Mysuru 570015, KA, India.
Musthafa Mohamed Essa Department of Food Science and Nutrition, CAMS, Sultan Qaboos University, Muscat 123, Oman; Ageing and Dementia Research Group, Sultan Qaboos University, Muscat 123, Oman; Biomedical Sciences Department, University of Pacific, Sacramento, CA, USA.
A G Rathipriya Food and Brain Research Foundation, Chennai 600 094, Tamil Nadu, India
Muhammed Bishir Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Mysuru 570015, KA, India
Bipul Ray Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Mysuru 570015, KA, India; Centre for Experimental Pharmacology and Toxicology (CPT), JSS Academy of Higher Education & Research, Mysuru 570015, KA, India
Arehally M Mahalakshmi Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Mysuru 570015, KA, India
A H Tousif Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Mysuru 570015, KA, India; Centre for Experimental Pharmacology and Toxicology (CPT), JSS Academy of Higher Education & Research, Mysuru 570015, KA, India
Meena K Sakharkar College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK S7N 5A2, Canada
Rajpal Singh Kashyap Research Centre, Dr G. M. Taori Central India Institute of Medical Sciences (CIIMS), Nagpur, Maharashtra, India
Robert P Friedland Department of Neurology, University of Louisville, Louisville, KY 40292, USA
Tanya M Monaghan NIHR Nottingham Biomedical Research Centre, University of Nottingham, Nottingham NG7 2UH, UK; Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham NG7 2UH, UK.

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Gundamaraju R, Chong WC. Consequence of distinctive expression of MUC2 in colorectal cancers: How much is actually bad? Biochim Biophys Acta Rev Cancer 2021;1876:188579. [PMID: 34139275 DOI: 10.1016/j.bbcan.2021.188579] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2021] [Revised: 06/08/2021] [Accepted: 06/10/2021] [Indexed: 12/18/2022]

Bai D, Sun T, Zhao J, Du J, Bu X, Cao W, Zhao Y, Lu N. Oroxylin A maintains the colonic mucus barrier to reduce disease susceptibility by reconstituting a dietary fiber-deprived gut microbiota. Cancer Lett 2021;515:73-85. [PMID: 34052330 DOI: 10.1016/j.canlet.2021.05.018] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2021] [Revised: 05/17/2021] [Accepted: 05/20/2021] [Indexed: 12/16/2022]

Affiliation(s)

Dongsheng Bai State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Department of Physiology, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, People's Republic of China
Tifan Sun State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Department of Physiology, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, People's Republic of China
Jiawei Zhao State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Department of Physiology, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, People's Republic of China
Jiaying Du State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Department of Physiology, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, People's Republic of China
Xiumin Bu State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Department of Physiology, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, People's Republic of China
Wangjia Cao State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Department of Physiology, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, People's Republic of China
Yue Zhao State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Department of Physiology, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, People's Republic of China.
Na Lu State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Department of Physiology, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, People's Republic of China.

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Ten Hove AS, Seppen J, de Jonge WJ. Neuronal innervation of the intestinal crypt. Am J Physiol Gastrointest Liver Physiol 2021;320:G193-G205. [PMID: 33296267 DOI: 10.1152/ajpgi.00239.2020] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]

Krolevets TS, Livzan MA, Mozgovoy SI. The Role of the Microbiome and Intestinal Mucosal Barrier in the Development and Progression of Non-Alcoholic Fatty Liver Disease. RUSSIAN JOURNAL OF GASTROENTEROLOGY, HEPATOLOGY, COLOPROCTOLOGY 2020;30:42-48. [DOI: 10.22416/1382-4376-2020-30-5-42-48] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/17/2024]

Anti-inflammatory effects of monoterpenoids in rats with TNBS-induced colitis. PHARMANUTRITION 2020. [DOI: 10.1016/j.phanu.2020.100240] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]

Martinez-Carrasco R, Argüeso P, Fini ME. Dynasore protects ocular surface mucosal epithelia subjected to oxidative stress by maintaining UPR and calcium homeostasis. Free Radic Biol Med 2020;160:57-66. [PMID: 32791188 PMCID: PMC7704702 DOI: 10.1016/j.freeradbiomed.2020.07.002] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2020] [Revised: 06/02/2020] [Accepted: 07/02/2020] [Indexed: 02/06/2023]

Gao F, Fan H. Heat shock protein 5 and inflammatory bowel disease. Shijie Huaren Xiaohua Zazhi 2020;28:802-806. [DOI: 10.11569/wcjd.v28.i16.802] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open

Singh P, Sanchez-Fernandez LL, Ramiro-Cortijo D, Ochoa-Allemant P, Perides G, Liu Y, Medina-Morales E, Yakah W, Freedman SD, Martin CR. Maltodextrin-induced intestinal injury in a neonatal mouse model. Dis Model Mech 2020;13:dmm044776. [PMID: 32753526 PMCID: PMC7473650 DOI: 10.1242/dmm.044776] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2020] [Accepted: 07/17/2020] [Indexed: 12/14/2022] Open

Li C, Wang X, Sun S, Liu S, Huan Y, Li R, Liu Q, Cao H, Zhou T, Lei L, Liu M, Shen Z. Effects of a ready-to-eat cereal formula powder on glucose metabolism, inflammation, and gut microbiota in diabetic db/db mice. Food Sci Nutr 2020;8:4523-4533. [PMID: 32884732 PMCID: PMC7455957 DOI: 10.1002/fsn3.1761] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2020] [Revised: 06/09/2020] [Accepted: 06/15/2020] [Indexed: 12/17/2022] Open

Affiliation(s)

Caina Li State Key Laboratory of Bioactive Substances and Functions of Natural MedicinesKey Laboratory of Polymorphic Drugs of BeijingInstitute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
Xing Wang State Key Laboratory of Bioactive Substances and Functions of Natural MedicinesKey Laboratory of Polymorphic Drugs of BeijingInstitute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
Sujuan Sun State Key Laboratory of Bioactive Substances and Functions of Natural MedicinesKey Laboratory of Polymorphic Drugs of BeijingInstitute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
Shuainan Liu State Key Laboratory of Bioactive Substances and Functions of Natural MedicinesKey Laboratory of Polymorphic Drugs of BeijingInstitute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
Yi Huan State Key Laboratory of Bioactive Substances and Functions of Natural MedicinesKey Laboratory of Polymorphic Drugs of BeijingInstitute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
Rongcui Li State Key Laboratory of Bioactive Substances and Functions of Natural MedicinesKey Laboratory of Polymorphic Drugs of BeijingInstitute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
Quan Liu State Key Laboratory of Bioactive Substances and Functions of Natural MedicinesKey Laboratory of Polymorphic Drugs of BeijingInstitute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
Hui Cao State Key Laboratory of Bioactive Substances and Functions of Natural MedicinesKey Laboratory of Polymorphic Drugs of BeijingInstitute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
Tian Zhou State Key Laboratory of Bioactive Substances and Functions of Natural MedicinesKey Laboratory of Polymorphic Drugs of BeijingInstitute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
Lei Lei State Key Laboratory of Bioactive Substances and Functions of Natural MedicinesKey Laboratory of Polymorphic Drugs of BeijingInstitute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
Minzhi Liu State Key Laboratory of Bioactive Substances and Functions of Natural MedicinesKey Laboratory of Polymorphic Drugs of BeijingInstitute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
Zhufang Shen State Key Laboratory of Bioactive Substances and Functions of Natural MedicinesKey Laboratory of Polymorphic Drugs of BeijingInstitute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

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Dotsenko V, Oittinen M, Taavela J, Popp A, Peräaho M, Staff S, Sarin J, Leon F, Isola J, Mäki M, Viiri K. Genome-Wide Transcriptomic Analysis of Intestinal Mucosa in Celiac Disease Patients on a Gluten-Free Diet and Postgluten Challenge. Cell Mol Gastroenterol Hepatol 2020;11:13-32. [PMID: 32745639 PMCID: PMC7593586 DOI: 10.1016/j.jcmgh.2020.07.010] [Citation(s) in RCA: 47] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2020] [Revised: 07/24/2020] [Accepted: 07/24/2020] [Indexed: 12/15/2022]

Abstract

BACKGROUND & AIMS

Gluten challenge studies are instrumental in understanding the pathophysiology of celiac disease. Our aims in this study were to reveal early gluten-induced transcriptomic changes in duodenal biopsies and to find tools for clinics.

METHODS

Duodenal biopsies were collected from 15 celiac disease patients on a strict long-term gluten-free diet (GFD) prior to and post a gluten challenge (PGC) and from 6 healthy control individuals (DC). Biopsy RNA was subjected to genome-wide 3' RNA-Seq. Sequencing data was used to determine the differences between the three groups and was compared to sequencing data from the public repositories. The biopsies underwent morphometric analyses.

RESULTS

In DC vs. GFD group comparisons, 167 differentially expressed genes were identified with 117 genes downregulated and 50 genes upregulated. In PGC vs. GFD group comparisons, 417 differentially expressed genes were identified with 195 genes downregulated and 222 genes upregulated. Celiac disease patients on a GFD were not "healthy". In particular, genes encoding proteins for transporting small molecules were expressed less. In addition to the activation of immune response genes, a gluten challenge induced hyperactive intestinal wnt-signaling and consequent immature crypt gene expression resulting in less differentiated epithelium. Biopsy gene expression in response to a gluten challenge correlated with the extent of the histological damage. Regression models using only four gene transcripts described 97.2% of the mucosal morphology and 98.0% of the inflammatory changes observed.

CONCLUSIONS

Our gluten challenge trial design provided an opportunity to study the transition from health to disease. The results show that even on a strict GFD, despite being deemed healthy, patients reveal patterns of ongoing disease. Here, a transcriptomic regression model estimating the extent of gluten-induced duodenal mucosal injury is presented.

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Affiliation(s)

Valeriia Dotsenko Tampere Center for Child Health Research, Faculty of Medicine and Health Technology, Tampere University Hospital, Tampere University Tampere, Finland
Mikko Oittinen Tampere Center for Child Health Research, Faculty of Medicine and Health Technology, Tampere University Hospital, Tampere University Tampere, Finland
Juha Taavela Tampere Center for Child Health Research, Faculty of Medicine and Health Technology, Tampere University Hospital, Tampere University Tampere, Finland,Department of Internal Medicine, Central Finland Central Hospital, Jyväskylä, Finland
Alina Popp Tampere Center for Child Health Research, Faculty of Medicine and Health Technology, Tampere University Hospital, Tampere University Tampere, Finland,Pediatric Department, Carol Davila University of Medicine and Pharmacy, Alessandrescu-Rusescu National Institute for Mother and Child Health, Bucharest, Romania
Markku Peräaho Department of Internal Medicine, Central Finland Central Hospital, Jyväskylä, Finland
Synnöve Staff Department of Obstetrics and Gynecology and Tays Cancer Centre, Faculty of Medicine and Health Technology, Tampere University Hospital, Tampere University, Tampere, Finland
Jani Sarin Laboratory of Cancer Biology, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland,Jilab Inc, Tampere, Finland
Francisco Leon Celimmune LLC, Bethesda, Maryland
Jorma Isola Laboratory of Cancer Biology, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland,Jilab Inc, Tampere, Finland
Markku Mäki Tampere Center for Child Health Research, Faculty of Medicine and Health Technology, Tampere University Hospital, Tampere University Tampere, Finland
Keijo Viiri Tampere Center for Child Health Research, Faculty of Medicine and Health Technology, Tampere University Hospital, Tampere University Tampere, Finland,Correspondence Address correspondence to: Keijo Viiri, PhD, Faculty of Medicine and Health Technology, Tampere University and Tampere University Hospital, Arvo Ylpön katu 34, Tampere, FIN-33520, Finland; fax: +35833641369.

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Potential role of ovomucin and its peptides in modulation of intestinal health: A review. Int J Biol Macromol 2020;162:385-393. [PMID: 32569696 PMCID: PMC7305749 DOI: 10.1016/j.ijbiomac.2020.06.148] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2020] [Revised: 06/11/2020] [Accepted: 06/16/2020] [Indexed: 01/06/2023]

Li CN, Wang X, Lei L, Liu MZ, Li RC, Sun SJ, Liu SN, Huan Y, Zhou T, Liu Q, Cao H, Bai GL, Han YW, Shen ZF. Berberine combined with stachyose induces better glycometabolism than berberine alone through modulating gut microbiota and fecal metabolomics in diabetic mice. Phytother Res 2019;34:1166-1174. [PMID: 31833107 PMCID: PMC7216932 DOI: 10.1002/ptr.6588] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2019] [Revised: 10/17/2019] [Accepted: 11/24/2019] [Indexed: 01/19/2023]

Affiliation(s)

Cai-Na Li State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Key laboratory of Polymorphic Drugs of Beijing, Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
Xing Wang State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Key laboratory of Polymorphic Drugs of Beijing, Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
Lei Lei State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Key laboratory of Polymorphic Drugs of Beijing, Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
Min-Zhi Liu State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Key laboratory of Polymorphic Drugs of Beijing, Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
Rong-Cui Li State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Key laboratory of Polymorphic Drugs of Beijing, Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
Su-Juan Sun State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Key laboratory of Polymorphic Drugs of Beijing, Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
Shuai-Nan Liu State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Key laboratory of Polymorphic Drugs of Beijing, Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
Yi Huan State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Key laboratory of Polymorphic Drugs of Beijing, Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
Tian Zhou State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Key laboratory of Polymorphic Drugs of Beijing, Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
Quan Liu State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Key laboratory of Polymorphic Drugs of Beijing, Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
Hui Cao State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Key laboratory of Polymorphic Drugs of Beijing, Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
Guo-Liang Bai State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Key laboratory of Polymorphic Drugs of Beijing, Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
Yu-Wei Han State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Key laboratory of Polymorphic Drugs of Beijing, Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
Zhu-Fang Shen State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Key laboratory of Polymorphic Drugs of Beijing, Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China

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