Dietary lipids containing gangliosides reduceGiardia murisinfectionin vivoand survival ofGiardia lambliatrophozoitesin vitro

Parasitology ◽  
2004 ◽  
Vol 128 (6) ◽  
pp. 595-602 ◽  
Author(s):  
M. SUH ◽  
M. BELOSEVIC ◽  
M. T. CLANDININ
Keyword(s):  
Small Intestine ◽  
Giardia Lamblia ◽  
Control Diet ◽  
Dietary Lipids ◽  
Gastric Intubation ◽  
Fat Composition ◽  
High Level ◽  
Giardia Muris

We examined whether a ganglioside supplemented diet affected the course ofGiardia murisinfection in mice and survival ofGiardia lambliatrophozoitesin vitro. Female CD-1 mice were fed 1 of 5 experimental diets: standard lab chow as a control diet; semi-synthetic diets containing 20% (w/w) triglyceride based on the fat composition of a conventional infant formula; triglyceride diet; triglyceride diet containing a low level of ganglioside (0·1% w/w); and triglyceride diet containing a high level of ganglioside (1·0% w/w of diet). After 2 weeks of feeding, mice were inoculated withG. murisby gastric intubation and fed the experimental diets during the course of the infection. Cysts released in the faeces and trophozoites present in the small intestine were enumerated at various times post-infection. The average cyst output and the number of trophozoites during the course of the infection in mice fed ganglioside-containing diet were found to be significantly lower (3-log10reduction) compared to animals fed control diets. The results ofin vitrogrowth studies indicated that gangliosides may be directly toxic to the parasites. Thus, gangliosides have a protective effect againstG. murisinfectionin vivoand affect the survival ofG. lambliatrophozoitesin vitro.

scholarly journals Intestinal miRNAs regulated in response to dietary lipids

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Judit Gil-Zamorano ◽  
João Tomé-Carneiro ◽  
María-Carmen Lopez de las Hazas ◽  
Lorena del Pozo-Acebo ◽  
M. Carmen Crespo ◽  
...  
Keyword(s):  
Small Intestine ◽  
Lipid Metabolism ◽  
Chronic Exposure ◽  
Potential Role ◽  
In Vitro Models ◽  
Dietary Lipids ◽  
Metabolism Regulation

Abstract The role of miRNAs in intestinal lipid metabolism is poorly described. The small intestine is constantly exposed to high amounts of dietary lipids, and it is under conditions of stress that the functions of miRNAs become especially pronounced. Approaches consisting in either a chronic exposure to cholesterol and triglyceride rich diets (for several days or weeks) or an acute lipid challenge were employed in the search for intestinal miRNAs with a potential role in lipid metabolism regulation. According to our results, changes in miRNA expression in response to fat ingestion are dependent on factors such as time upon exposure, gender and small intestine section. Classic and recent intestinal in vitro models (i.e. differentiated Caco-2 cells and murine organoids) partially mirror miRNA modulation in response to lipid challenges in vivo. Moreover, intestinal miRNAs might play a role in triglyceride absorption and produce changes in lipid accumulation in intestinal tissues as seen in a generated intestinal Dicer1-deletion murine model. Overall, despite some variability between the different experimental cohorts and in vitro models, results show that some miRNAs analysed here are modulated in response to dietary lipids, hence likely to participate in the regulation of lipid metabolism, and call for further research.

scholarly journals Broiler chicken body weights, feed intakes, plasma lipid and small-intestinal bile acid concentrations in response to feeding of chitosan and pectin

1997 ◽  
Vol 78 (2) ◽  
pp. 283-291 ◽  
Author(s):  
A. Razdan ◽  
D. Pettersson ◽  
J. Pettersson
Keyword(s):  
Small Intestine ◽  
Bile Acid ◽  
Broiler Chicken ◽  
Plasma Cholesterol ◽  
Control Diet ◽  
Plasma Lipid ◽  
Cholesterol Ratio ◽  
Body Weights

One-day-old broiler chickens were fed on a control diet based on maize and maize starch or diets containing 30g/kg of 89 % deacetylated chitin (chitosan) or low-methoxyl (34 % degree of esterification) pectin. Feeding of the chitosan diet to chickens significantly reduced body weights and feed intakes compared with animals fed on control or pectin diets on days 5 and 11 of the experiment. On day 12, significant reductions in total plasma cholesterol and HDL-cholesterol concentrations were observed among birds fed on the chitosan but not the pectin diet in relation to control-fed animals. A concomitant increase in the plasma HDL-cholesterol:total cholesterol ratio was observed among chitosan-fed chickens. The generally reduced concentrations of primary and total bile acids in the duodenum of birds fed on the fibre-containing diets on day 13 may have been an indication of a delay in the production and/or secretion of bile. Viscosity of the three broiler-chicken diets was measured after suspension in water, acidification and finally neutralization of the suspensions, in an attempt to simulate the effect of changes in pH and dilution of diets occurring in the gizzard and small intestine of chickens. Viscosity of the chitosan diet was significantly elevated after acidification and significantly reduced at neutralization in comparison with the control and pectin-containingdiets suggesting that the hypolipidaemic influence of chitosan observed in the present study may be due to interruption of enterohepatic bile acid circulation rather than increased viscosity in the small intestine of chickens. The low viscosity of the pectin dietin vitrotogether with the absence of a hypocholesterolaemic effect of this diet when fedin vivoprecludes any conclusion regarding the hypocholesterolaemic mechanism of pectin observed in earlier studies.

scholarly journals Impaired Parasite Attachment as Fitness Cost of Metronidazole Resistance in Giardia lamblia

2011 ◽  
Vol 55 (10) ◽  
pp. 4643-4651 ◽  
Author(s):  
Noa Tejman-Yarden ◽  
Maya Millman ◽  
Tineke Lauwaet ◽  
Barbara J. Davids ◽  
Frances D. Gillin ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Cell Lines ◽  
Giardia Lamblia ◽  
Cross Resistance ◽  
Content Type ◽  
Metronidazole Resistance ◽  
High Level ◽  
Plastic Surfaces

ABSTRACTInfections with the diarrheagenic protozoan pathogenGiardia lambliaare most commonly treated with metronidazole (Mz). Treatment failures with Mz occur in 10 to 20% of cases and Mz resistance develops in the laboratory, yet clinically, Mz-resistant (Mzr)G. lambliahas rarely been isolated from patients. To understand why clinical Mzrisolates are rare, we questioned whether Mz resistance entails fitness costs to the parasite. Our studies employed several newly generated and established isogenic Mzrcell lines with stable, high-level resistance to Mz and significant cross-resistance to tinidazole, nitazoxanide, and furazolidone. Oral infection of suckling mice revealed that three of five Mzrcell lines could not establish infection, while two Mzrcell lines infected pups, albeit with reduced efficiencies. Failure to colonize resulted from a diminished capacity of the parasite to attach to the intestinal mucosain vivoand to epithelial cells and plastic surfacesin vitro. The attachment defect was related to impaired glucose metabolism, since the noninfectious Mzrlines consumed less glucose, and glucose promoted ATP-independent parasite attachment in the parental lines. Thus, resistance ofGiardiato Mz is accompanied by a glucose metabolism-related attachment defect that can interfere with colonization of the host. Because glucose-metabolizing pathways are important for activation of the prodrug Mz, it follows that a fitness trade-off exists between diminished Mz activation and reduced infectivity, which may explain the observed paucity of clinical Mzrisolates ofGiardia. However, the data also caution that some forms of Mz resistance do not markedly interfere within vivoinfectivity.

scholarly journals Aberrantly high activation of a FoxM1–STMN1 axis contributes to progression and tumorigenesis in FoxM1-driven cancers

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Jun Liu ◽  
Jipeng Li ◽  
Ke Wang ◽  
Haiming Liu ◽  
Jianyong Sun ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Poor Prognosis ◽  
Soft Agar ◽  
Transcriptional Level ◽  
Regulation Mechanism ◽  
Strong Positive Correlation ◽  
Cell Viability Assay ◽  
High Level

AbstractFork-head box protein M1 (FoxM1) is a transcriptional factor which plays critical roles in cancer development and progression. However, the general regulatory mechanism of FoxM1 is still limited. STMN1 is a microtubule-binding protein which can inhibit the assembly of microtubule dimer or promote depolymerization of microtubules. It was reported as a major responsive factor of paclitaxel resistance for clinical chemotherapy of tumor patients. But the function of abnormally high level of STMN1 and its regulation mechanism in cancer cells remain unclear. In this study, we used public database and tissue microarrays to analyze the expression pattern of FoxM1 and STMN1 and found a strong positive correlation between FoxM1 and STMN1 in multiple types of cancer. Lentivirus-mediated FoxM1/STMN1-knockdown cell lines were established to study the function of FoxM1/STMN1 by performing cell viability assay, plate clone formation assay, soft agar assay in vitro and xenograft mouse model in vivo. Our results showed that FoxM1 promotes cell proliferation by upregulating STMN1. Further ChIP assay showed that FoxM1 upregulates STMN1 in a transcriptional level. Prognostic analysis showed that a high level of FoxM1 and STMN1 is related to poor prognosis in solid tumors. Moreover, a high co-expression of FoxM1 and STMN1 has a more significant correlation with poor prognosis. Our findings suggest that a general FoxM1-STMN1 axis contributes to cell proliferation and tumorigenesis in hepatocellular carcinoma, gastric cancer and colorectal cancer. The combination of FoxM1 and STMN1 can be a more precise biomarker for prognostic prediction.

scholarly journals MiR-211 determines brain metastasis specificity through SOX11/NGN2 axis in triple-negative breast cancer

Oncogene ◽  
2021 ◽  
Author(s):  
Jhih-Kai Pan ◽  
Cheng-Han Lin ◽  
Yao-Lung Kuo ◽  
Luo-Ping Ger ◽  
Hui-Chuan Cheng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastasis ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Survival Outcomes ◽  
Poor Survival ◽  
Breast Cancer Brain Metastasis ◽  
High Level

AbstractBrian metastasis, which is diagnosed in 30% of triple-negative breast cancer (TNBC) patients with metastasis, causes poor survival outcomes. Growing evidence has characterized miRNAs involving in breast cancer brain metastasis; however, currently, there is a lack of prognostic plasma-based indicator for brain metastasis. In this study, high level of miR-211 can act as brain metastatic prognostic marker in vivo. High miR-211 drives early and specific brain colonization through enhancing trans-blood–brain barrier (BBB) migration, BBB adherence, and stemness properties of tumor cells and causes poor survival in vivo. SOX11 and NGN2 are the downstream targets of miR-211 and negatively regulate miR-211-mediated TNBC brain metastasis in vitro and in vivo. Most importantly, high miR-211 is correlated with poor survival and brain metastasis in TNBC patients. Our findings suggest that miR-211 may be used as an indicator for TNBC brain metastasis.

scholarly journals Generation of tetracycline-controllable CYP3A4-expressing Caco-2 cells by the piggyBac transposon system

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Moe Ichikawa ◽  
Hiroki Akamine ◽  
Michika Murata ◽  
Sumito Ito ◽  
Kazuo Takayama ◽  
...  
Keyword(s):  
Small Intestine ◽  
Drug Absorption ◽  
Cell Model ◽  
Negative Effects ◽  
Piggybac Transposon ◽  
Drug Metabolizing Enzyme ◽  
Metabolizing Enzyme ◽  
Cyp3a4 Expression

AbstractCaco-2 cells are widely used as an in vitro intestinal epithelial cell model because they can form a monolayer and predict drug absorption with high accuracy. However, Caco-2 cells hardly express cytochrome P450 (CYP), a drug-metabolizing enzyme. It is known that CYP3A4 is the dominant drug-metabolizing enzyme in human small intestine. In this study, we generated CYP3A4-expressing Caco-2 (CYP3A4-Caco-2) cells and attempted to establish a model that can simultaneously evaluate drug absorption and metabolism. CYP3A4-Caco-2 cells were generated by piggyBac transposon vectors. A tetracycline-controllable CYP3A4 expression cassette (tet-on system) was stably transduced into Caco-2 cells, thus regulating the levels of CYP3A4 expression depending on the doxycycline concentration. The CYP3A4 expression levels in CYP3A4-Caco-2 cells cultured in the presence of doxycycline were similar to or higher than those of adult small intestine. The CYP3A4-Caco-2 cells had enough ability to metabolize midazolam, a substrate of CYP3A4. CYP3A4 overexpression had no negative effects on cell proliferation, barrier function, and P-glycoprotein activity in Caco-2 cells. Thus, we succeeded in establishing Caco-2 cells with CYP3A4 metabolizing activity comparable to in vivo human intestinal tissue. This cell line would be useful in pharmaceutical studies as a model that can simultaneously evaluate drug absorption and metabolism.

scholarly journals LINC00680 enhances hepatocellular carcinoma stemness behavior and chemoresistance by sponging miR-568 to upregulate AKT3

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Gege Shu ◽  
Huizhao Su ◽  
Zhiqian Wang ◽  
Shihui Lai ◽  
Yan Wang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Xenograft Model ◽  
Luciferase Reporter ◽  
Loss Of Function ◽  
Mechanism Study ◽  
Downstream Signaling ◽  
Mouse Xenograft Model ◽  
High Level

Abstract Background Hepatocellular carcinoma (HCC) has an extremely poor prognosis due to the development of chemoresistance, coupled with inherently increased stemness properties. Long non-coding RNAs (LncRNAs) are key regulators for tumor cell stemness and chemosensitivity. Currently the relevance between LINC00680 and tumor progression was still largely unknown, with only one study showing its significance in glioblastoma. The study herein was aimed at identifying the role of LINC00680 in the regulation HCC stemness and chemosensitivity. Methods QRT-PCR was used to detect the expression of LINC00680, miR-568 and AKT3 in tissue specimen and cell lines. Gain- or loss-of function assays were applied to access the function of LINC00680 in HCC cells, including cell proliferation and stemness properties. HCC stemness and chemosensitivity were determined by sphere formation, cell viability and colony formation. Luciferase reporter, RNA immunoprecipitation (RIP), and RNA pull-down assays were performed to examine the interaction between LINC00680 and miR-568 as well as that between miR-568 and AKT3. A nude mouse xenograft model was established for the in vivo study. Results We found that LINC00680 was remarkably upregulated in HCC tissues. Patients with high level of LINC00680 had poorer prognosis. LINC00680 overexpression significantly enhanced HCC cell stemness and decreased in vitro and in vivo chemosensitivity to 5-fluorouracil (5-Fu), whereas LINC00680 knockdown led to opposite results. Mechanism study revealed that LINC00680 regulated HCC stemness and chemosensitivity through sponging miR-568, thereby expediting the expression of AKT3, which further activated its downstream signaling molecules, including mTOR, elF4EBP1, and p70S6K. Conclusion LINC00680 promotes HCC stemness properties and decreases chemosensitivity through sponging miR-568 to activate AKT3, suggesting that LINC00680 might be a potentially important HCC diagnosis marker and therapeutic target.

scholarly journals Absorption of lactulose from mammalian gastrointestinal tract

1979 ◽  
Vol 41 (1) ◽  
pp. 47-51 ◽  
Author(s):  
D. F. Evered ◽  
F. Sadoogh-Abasian
Keyword(s):  
Small Intestine ◽  
Calcium Ions ◽  
Clinical Evidence ◽  
Buccal Cavity ◽  
Rat Small Intestine ◽  
Sodium Ions ◽  
Mode Of Transport ◽  
Poor Absorption

1. The disaccharide lactulose (galactosyl-β-1,4-fructose) was poorly absorbed from rat small intestine in vitro and human mouth in vivo.2. These results confirm indirect clinical evidence of poor absorption from the intestine.3. The presence of calcium ions, or absence of sodium ions, had no effect on lactulose absorption from the buccal cavity.4. The presence of ouabain, or absence of Na+, did not decrease the absorption of lactulose from small intestine.5. It is thought that the mode of transport, in both instances, is by passive diffusion with the concentration gradient.

scholarly journals Porcine Milk-Derived Small Extracellular Vesicles Promote Intestinal Immunoglobulin Production through pIgR

Animals ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1522
Author(s):  
Bin Zeng ◽  
Hailong Wang ◽  
Junyi Luo ◽  
Meiying Xie ◽  
Zhengjiang Zhao ◽  
...  
Keyword(s):  
Small Intestine ◽  
Extracellular Vesicles ◽  
Immunoglobulin A ◽  
Luciferase Reporter ◽  
Epithelial Cell Line ◽  
Intestinal Immunity ◽  
In Vivo Experiments ◽  
Porcine Milk

Secretory immunoglobulin A (SIgA) plays an important role in gut acquired immunity and mucosal homeostasis. Breast milk is the irreplaceable nutritional source for mammals after birth. Current studies have shown the potential functional role of milk-derived small extracellular vesicles (sEVs) and their RNAs cargo in intestinal health and immune regulation. However, there is a lack of studies to demonstrate how milk-derived sEVs affect intestinal immunity in recipient. In this study, through in vivo experiments, we found that porcine milk small extracellular vesicles (PM-sEVs) promoted intestinal SIgA levels, and increased the expression levels of polymeric immunoglobulin receptor (pIgR) both in mice and piglet. We examined the mechanism of how PM-sEVs increased the expression level of pIgR in vitro by using a porcine small intestine epithelial cell line (IPEC-J2). Through bioinformatics analysis, dual-luciferase reporter assays, and overexpression or knockdown of the corresponding non-coding RNAs, we identified circ-XPO4 in PM-sEVs as a crucial circRNA, which leads to the expression of pIgR via the suppression of miR-221-5p in intestinal cells. Importantly, we also observed that oral administration of PM-sEVs increased the level of circ-XPO4 and decreased the level of miR-221-5p in small intestine of piglets, indicating that circRNAs in milk-derived sEVs act as sponge for miRNAs in recipients. This study, for the first time, reveals that PM-sEVs have a capacity to stimulate intestinal SIgA production by delivering circRNAs to receptors and sponging the recipient’s original miRNAs, and also provides valuable data for insight into the role and mechanism of animal milk sEVs in intestinal immunity.

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