Soy diet induces intestinal inflammation in adult Zebrafish: Role of OTX and P53 family

Herein, we investigate whether: (1) the administration of glucose or a lipid emulsion is useful in liver transplantation (LT) using steatotic (induced genetically or nutritionally) or non-steatotic livers from donors after brain death (DBDs); and (2) any such benefits are due to reductions in intestinal damage and consequently to gut microbiota preservation. In recipients from DBDs, we show increased hepatic damage and failure in the maintenance of ATP, glycogen, phospholipid and growth factor (HGF, IGF1 and VEGFA) levels, compared to recipients from non-DBDs. In recipients of non-steatotic grafts from DBDs, the administration of glucose or lipids did not protect against hepatic damage. This was associated with unchanged ATP, glycogen, phospholipid and growth factor levels. However, the administration of lipids in steatotic grafts from DBDs protected against damage and ATP and glycogen drop and increased phospholipid levels. This was associated with increases in growth factors. In all recipients from DBDs, intestinal inflammation and damage (evaluated by LPS, vascular permeability, mucosal damage, TLR4, TNF, IL1, IL-10, MPO, MDA and edema formation) was not shown. In such cases, potential changes in gut microbiota would not be relevant since neither inflammation nor damage was evidenced in the intestine following LT in any of the groups evaluated. In conclusion, lipid treatment is the preferable nutritional support to protect against hepatic damage in steatotic LT from DBDs; the benefits were independent of alterations in the recipient intestine.

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Helminth Interactions with Bacteria in the Host Gut Are Essential for Its Immunomodulatory Effect

Microorganisms ◽

10.3390/microorganisms9020226 ◽

2021 ◽

Vol 9 (2) ◽

pp. 226

Author(s):

Milan Jirků ◽

Zuzana Lhotská ◽

Lucia Frgelecová ◽

Oldřiška Kadlecová ◽

Klára Judita Petrželková ◽

...

Keyword(s):

Protective Effect ◽

Intestinal Inflammation ◽

Hymenolepis Diminuta ◽

Clinical Parameters ◽

Th2 Response ◽

Histological Changes ◽

Immunological Markers ◽

Bacterial Microbiota ◽

Inflammatory Effect

Colonization by the benign tapeworm, Hymenolepis diminuta, has been associated with a reduction in intestinal inflammation and changes in bacterial microbiota. However, the role of microbiota in the tapeworm anti-inflammatory effect is not yet clear, and the aim of this study was to determine whether disruption of the microflora during worm colonization can affect the course of intestinal inflammation. We added a phase for disrupting the intestinal microbiota using antibiotics to the experimental design for which we previously demonstrated the protective effect of H. diminuta. We monitored the immunological markers, clinical parameters, bacterial microbiota, and histological changes in the colon of rats. After a combination of colonization, antibiotics, and colitis induction, we had four differently affected experimental groups. We observed a different course of the immune response in each group, but no protective effect was found. Rats treated with colonization and antibiotics showed a strong induction of the Th2 response as well as a significant change in microbial diversity. The microbial results also revealed differences in the richness and abundance of some bacterial taxa, influenced by various factors. Our data suggest that interactions between the tapeworm and bacteria may have a major impact on its protective effect.

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Inhibition of let-7c Regulates Cardiac Regeneration after Cryoinjury in Adult Zebrafish

Journal of Cardiovascular Development and Disease ◽

10.3390/jcdd6020016 ◽

2019 ◽

Vol 6 (2) ◽

pp. 16 ◽

Cited By ~ 1

Author(s):

Suneeta Narumanchi ◽

Karri Kalervo ◽

Sanni Perttunen ◽

Hong Wang ◽

Katariina Immonen ◽

...

Keyword(s):

Cardiac Function ◽

Cardiac Regeneration ◽

Nuclear Antigen ◽

Heart Regeneration ◽

Adult Zebrafish ◽

Tissue Samples ◽

Micro Rnas ◽

Proliferating Cell ◽

Zebrafish Heart

The let-7c family of micro-RNAs (miRNAs) is expressed during embryonic development and plays an important role in cell differentiation. We have investigated the role of let-7c in heart regeneration after injury in adult zebrafish. let-7c antagomir or scramble injections were given at one day after cryoinjury (1 dpi). Tissue samples were collected at 7 dpi, 14 dpi and 28 dpi and cardiac function was assessed before cryoinjury, 1 dpi, 7 dpi, 14 dpi and 28 dpi. Inhibition of let-7c increased the rate of fibrinolysis, increased the number of proliferating cell nuclear antigen (PCNA) positive cardiomyocytes at 7 dpi and increased the expression of the epicardial marker raldh2 at 7 dpi. Additionally, cardiac function measured with echocardiography recovered slightly more rapidly after inhibition of let-7c. These results reveal a beneficial role of let-7c inhibition in adult zebrafish heart regeneration.

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A zebrafish model of infection-associated acute kidney injury

AJP Renal Physiology ◽

10.1152/ajprenal.00328.2017 ◽

2018 ◽

Vol 315 (2) ◽

pp. F291-F299 ◽

Cited By ~ 7

Author(s):

Xiaoyan Wen ◽

Liyan Cui ◽

Seth Morrisroe ◽

Donald Maberry ◽

David Emlet ◽

...

Keyword(s):

Acute Kidney Injury ◽

Unmet Need ◽

Kidney Injury ◽

Edwardsiella Tarda ◽

Adult Zebrafish ◽

Zebrafish Model ◽

Pericardial Edema ◽

Kidney Injury Molecule 1 ◽

Dose Dependent

Sepsis-associated acute kidney injury (S-AKI) independently predicts mortality among critically ill patients. The role of innate immunity in this process is unclear, and there is an unmet need for S-AKI models to delineate the pathophysiological response. Mammals and zebrafish ( Danio rerio) share a conserved nephron structure and homologous innate immune systems, making the latter suitable for S-AKI research. We introduced Edwardsiella tarda to the zebrafish. Systemic E. tarda bacteremia resulted in sustained bacterial infection and dose-dependent mortality. A systemic immune reaction was characterized by increased mRNA expressions of il1b, tnfa, tgfb1a, and cxcl8-l1 ( P < 0.0001, P < 0.001, P < 0.001, and P < 0.01, respectively). Increase of host stress response genes ccnd1 and tp53 was observed at 24 h postinjection ( P < 0.0001 and P < 0.05, respectively). Moderate E. tarda infection induced zebrafish mortality of over 50% in larvae and 20% in adults, accompanied by pericardial edema in larvae and renal dysfunction in both larval and adult zebrafish. Expression of AKI markers insulin-like growth factor-binding protein-7 (IGFBP7), tissue inhibitor of metalloproteinases 2 (TIMP-2), and kidney injury molecule-1 (KIM-1) was found to be significantly increased in the septic animals at the transcription level ( P < 0.01, P < 0.05, and P < 0.05) and in nephric tubules compared with noninfected animals. In conclusion, we established a zebrafish model of S-AKI induced by E. tarda injection, with both larval and adult zebrafish showing nephron injury in the setting of infection.

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O-031 The Complex Role of IL-36γ during Intestinal Inflammation

Inflammatory Bowel Diseases ◽

10.1097/01.mib.0000438582.65539.24 ◽

2013 ◽

Vol 19 ◽

pp. S17

Author(s):

Oscar Medina-Contreras ◽

Duke Geem ◽

Timothy Denning

Keyword(s):

Intestinal Inflammation

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Role of the Helicobacter hepaticus Flagellar Sigma Factor FliA in Gene Regulation and Murine Colonization

Journal of Bacteriology ◽

10.1128/jb.00626-08 ◽

2008 ◽

Vol 190 (19) ◽

pp. 6398-6408 ◽

Cited By ~ 15

Author(s):

Torsten Sterzenbach ◽

Lucie Bartonickova ◽

Wiebke Behrens ◽

Birgit Brenneke ◽

Jessika Schulze ◽

...

Keyword(s):

Gene Regulation ◽

Sigma Factor ◽

Intestinal Inflammation ◽

Gall Stone ◽

Helicobacter Hepaticus ◽

Intestinal Colonization ◽

Wild Type ◽

Chronic Intestinal Inflammation ◽

Flagellar Genes

ABSTRACT The enterohepatic Helicobacter species Helicobacter hepaticus colonizes the murine intestinal and hepatobiliary tract and is associated with chronic intestinal inflammation, gall stone formation, hepatitis, and hepatocellular carcinoma. Thus far, the role of H. hepaticus motility and flagella in intestinal colonization is unknown. In other, closely related bacteria, late flagellar genes are mainly regulated by the sigma factor FliA (σ28). We investigated the function of the H. hepaticus FliA in gene regulation, flagellar biosynthesis, motility, and murine colonization. Competitive microarray analysis of the wild type versus an isogenic fliA mutant revealed that 11 genes were significantly more highly expressed in wild-type bacteria and 2 genes were significantly more highly expressed in the fliA mutant. Most of these were flagellar genes, but four novel FliA-regulated genes of unknown function were identified. H. hepaticus possesses two identical copies of the gene encoding the FliA-dependent major flagellin subunit FlaA (open reading frames HH1364 and HH1653). We characterized the phenotypes of mutants in which fliA or one or both copies of the flaA gene were knocked out. flaA_1 flaA_2 double mutants and fliA mutants did not synthesize detectable amounts of FlaA and possessed severely truncated flagella. Also, both mutants were nonmotile and unable to colonize mice. Mutants with either flaA gene knocked out produced flagella morphologically similar to those of wild-type bacteria and expressed FlaA and FlaB. flaA_1 mutants which had flagella but displayed reduced motility did not colonize mice, indicating that motility is required for intestinal colonization by H. hepaticus and that the presence of flagella alone is not sufficient.

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Neuropeptide Y (NPY) promotes inflammation-induced tumorigenesis by enhancing epithelial cell proliferation

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00410.2015 ◽

2017 ◽

Vol 312 (2) ◽

pp. G103-G111 ◽

Cited By ~ 12

Author(s):

Sabrina Jeppsson ◽

Shanthi Srinivasan ◽

Bindu Chandrasekharan

Keyword(s):

Cell Proliferation ◽

Epithelial Cell ◽

Neuropeptide Y ◽

Intestinal Inflammation ◽

Enteric Neurons ◽

Intestinal Epithelial ◽

Epithelial Proliferation ◽

Proliferation And Apoptosis

We have demonstrated that neuropeptide Y (NPY), abundantly produced by enteric neurons, is an important regulator of intestinal inflammation. However, the role of NPY in the progression of chronic inflammation to tumorigenesis is unknown. We investigated whether NPY could modulate epithelial cell proliferation and apoptosis, and thus regulate tumorigenesis. Repeated cycles of dextran sodium sulfate (DSS) were used to model inflammation-induced tumorigenesis in wild-type (WT) and NPY knockout ( NPY−/−) mice. Intestinal epithelial cell lines (T84) were used to assess the effects of NPY (0.1 µM) on epithelial proliferation and apoptosis in vitro. DSS-WT mice exhibited enhanced intestinal inflammation, polyp size, and polyp number (7.5 ± 0.8) compared with DSS- NPY−/− mice (4 ± 0.5, P < 0.01). Accordingly, DSS-WT mice also showed increased colonic epithelial proliferation (PCNA, Ki67) and reduced apoptosis (TUNEL) compared with DSS- NPY−/− mice. The apoptosis regulating microRNA, miR-375, was significantly downregulated in the colon of DSS-WT (2-fold, P < 0.01) compared with DSS- NPY−/−-mice. In vitro studies indicated that NPY promotes cell proliferation (increase in PCNA and β-catenin, P < 0.05) via phosphatidyl-inositol-3-kinase (PI3-K)-β-catenin signaling, suppressed miR-375 expression, and reduced apoptosis (increase in phospho-Bad). NPY-treated cells also displayed increased c-Myc and cyclin D1, and reduction in p21 ( P < 0.05). Addition of miR-375 inhibitor to cells already treated with NPY did not further enhance the effects induced by NPY alone. Our findings demonstrate a novel regulation of inflammation-induced tumorigenesis by NPY-epithelial cross talk as mediated by activation of PI3-K signaling and downregulation of miR-375. NEW & NOTEWORTHY Our work exemplifies a novel role of neuropeptide Y (NPY) in regulating inflammation-induced tumorigenesis via two modalities: first by enhanced proliferation (PI3-K/pAkt), and second by downregulation of microRNA-375 (miR-375)-dependent apoptosis in intestinal epithelial cells. Our data establish the existence of a microRNA-mediated cross talk between enteric neurons producing NPY and intestinal epithelial cells, and the potential of neuropeptide-regulated miRNAs as potential therapeutic molecules for the management of inflammation-associated tumors in the gut.

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Extracellular vesicles package dsDNA to aggravate Crohn’s disease by activating the STING pathway

Cell Death and Disease ◽

10.1038/s41419-021-04101-z ◽

2021 ◽

Vol 12 (9) ◽

Author(s):

Fan Zhao ◽

Tao Zheng ◽

Wenbin Gong ◽

Jie Wu ◽

Haohao Xie ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Extracellular Vesicles ◽

Intestinal Inflammation ◽

Therapeutic Effects ◽

Murine Colitis ◽

Sting Pathway ◽

Deficient Mice

AbstractCrohn’s disease (CD) is an intestinal immune-dysfunctional disease. Extracellular vesicles (EVs) are membrane-enclosed particles full of functional molecules, e.g., nuclear acids. Recently, EVs have been shown to participate in the development of CD by realizing intercellular communication among intestinal cells. However, the role of EVs carrying double-strand DNA (dsDNA) shed from sites of intestinal inflammation in CD has not been investigated. Here we isolated EVs from the plasma or colon lavage of murine colitis and CD patients. The level of exosomal dsDNA, including mtDNA and nDNA, significantly increased in murine colitis and active human CD, and was positively correlated with the disease activity. Moreover, the activation of the STING pathway was verified in CD. EVs from the plasma of active human CD triggered STING activation in macrophages in vitro. EVs from LPS-damaged colon epithelial cells were also shown to raise inflammation in macrophages via activating the STING pathway, but the effect disappeared after the removal of exosomal dsDNA. These findings were further confirmed in STING-deficient mice and macrophages. STING deficiency significantly ameliorated colitis. Besides, potential therapeutic effects of GW4869, an inhibitor of EVs release were assessed. The application of GW4869 successfully ameliorated murine colitis by inhibiting STING activation. In conclusion, exosomal dsDNA was found to promote intestinal inflammation via activating the STING pathway in macrophages and act as a potential mechanistic biomarker and therapeutic target of CD.

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Obesity and inflammatory bowel disease

Gastroenterologie a hepatologie ◽

10.48095/ccgh202120 ◽

2021 ◽

Vol 75 (1) ◽

pp. 20-28

Author(s):

Vladimír Teplan ◽

Milan Lukáš

Keyword(s):

Inflammatory Bowel Disease ◽

Adipose Tissue ◽

Bowel Disease ◽

Intestinal Inflammation ◽

Perioperative Complications ◽

Overweight And Obesity ◽

Special Role ◽

Low Concentrations ◽

Inflammatory Bowel

The incidence and prevalence of overweight and obesity has dramatically increased in the last decades and is generally considered to be global pandemics. The incidence of inflammatory bowel disease (IBD) is rising parallel with overweight and obesity. Contrary to a conventional believe, about 15–40% patients with IBD are obese, which can contribute to the development and course of IBD, especially in Crohn’s disease. Although the findings of some cohort studies are still conflicting, recent results indicate a special role of visceral adipose tissue and particularly mesenteric adipose tissue known as creeping fat, leading to intestinal inflammation. The involvement of altered adipocyte function and deregulated production of adipokines such as leptin and adiponectin has been suggested in the pathogenesis of IBD. The emerging role of Western diet and microbiota can also open new possibilities in IBD management. The effect of obesity on the IBD-related therapy remains to be studied. The finding that obesity results in suboptimal response to the therapy, potentially promoting rapid clearance of biologic agents and thus leading to their low concentrations, has a great importance. Obesity also makes IBD colorectal surgery technically challenging and might increase a risk of perioperative complications.

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