Intestinal Mucin Research Articles

MYC aberrations in AC and PDA

Introduction: The aim of our study was investigation of the presence of MYC amplification in PDA and carcinoma of the vater. Method: 74 cases of PDA, 15 cases of cancer of the vater and seven cases of control pancreatic tissue were included in the study. We examined the expression of MUC1, 2 and 5AC types by immunohistochemical analyses in PDA and carcinoma of the vater. Dual-color interphase fluorescent in situ hybridization (FISH) was performed on 4-μm thick sections of formalin-fixed paraffin-embedded (FFPE) tumors. Results: Most of the PDA have been reported as - MUC1 + / MUC5AC + and accounted for 42% (31/74), the smallest was a group with the intestinal mucin phenotype (MUC2 +) and only 7% (5/74). The group with the gastric phenotype (MUC5AC +) was - 15% (11/74). Carcinoma of the vater in most cases have been reported as MUC2 + and accounted for 80% (12/15), 20% (3/15) of cases the tumor presented as MUC1 + /MUC5AC +. In normal ducts of all 7 control cases the tested loci had balanced (diploid) profile. FISH analysis of PDA revealed of MYC gene copy number in 21/74 (28%) cases. Eight of the 74 pancreatic tumors (10,8%) revealed MYC gain in association with an increased chromosome 8 copy number. Conclusion: MYC gene amplification should be considered as a marker of a more aggressive behavior in cancers biliary pancreaticduodenal region. Diploid profile MYC gene in carcinomas of the vater indicates a more favorable prognosis compared with ductal adenocarcinomas of the pancreas.

L-Threonine improves intestinal mucin synthesis and immune function of intrauterine growth-retarded weanling piglets.

The aim of this study was to investigate the effects of dietary l-threonine supplementation on the growth performance, intestinal immune function, mucin synthesis, and goblet cell differentiation in weanling piglets with intrauterine growth retardation (IUGR). Eighteen litters of newborn piglets were selected at birth, with one normal birthweight (NBW) and two IUGR piglets in each litter. At weaning, the NBW piglet and one of the IUGR piglets were assigned to groups fed a basal diet (i.e., the NBW-CON and IUGR-CON groups). The other IUGR piglet was assigned to a group fed the basal diet supplemented with 2g l-threonine per kg of diet (i.e., IUGR-Thr group). Therefore, all piglets were distributed across three groups for a 3-wk feeding trial. Compared with NBW, IUGR decreased growth performance, increased ileal proinflammatory cytokine levels, and reduced ileal mucin 2 (Muc2) content and goblet cell density of weanling piglets. Supplementation of l-threonine increased the feed efficiency of the IUGR-Thr group compared with the IUGR-CON group. The l-threonine-supplemented diet attenuated ileal inflammatory responses of the IUGR-Thr piglets and increased production of Muc2 and secretory immunoglobulin A and density of goblet cells. In addition, L-threonine supplementation downregulated δ-like 1 and hes family bHLH transcription factor 1, whereas growth factor independence 1 and Kruppel-like factor 4 expression levels were upregulated. Dietary l-threonine supplementation attenuates inflammatory responses, facilitates Muc2 synthesis, and promotes goblet cell differentiation in the ileum of IUGR piglets.

Sodium butyrate ameliorates insulin resistance and renal failure in CKD rats by modulating intestinal permeability and mucin expression.

BackgroundThe associated increase in the lipopolysaccharide (LPS) levels and uremic toxins in chronic kidney disease (CKD) has shifted the way we focus on intestinal microbiota. This study shows that a disruption of the intestinal barrier in CKD promotes leakage of LPS from the gut, subsequently decreasing insulin sensitivity. Butyrate treatment improved the intestinal barrier function by increasing colonic mucin and tight junction (TJ) proteins. This modulation further ameliorated metabolic functions such as insulin intolerance and improved renal function.MethodsRenal failure was induced by 5/6th nephrectomy (Nx) in rats. A group of Nx and control rats received sodium butyrate in drinking water. The Nx groups were compared with sham-operated controls.ResultsThe Nx rats had significant increases in serum creatinine, urea and proteinuria. These animals had impaired glucose and insulin tolerance and increased gluconeogenesis, which corresponded with decreased glucagon-like peptide-1 (GLP-1) secretion. The Nx animals suffered significant loss of intestinal TJ proteins, colonic mucin and mucin 2 protein. This was associated with a significant increase in circulating LPS, suggesting a leaky gut phenomenon. 5′adenosine monophosphate-activated protein kinase (AMPK) phosphorylation, known to modulate epithelial TJs and glucose metabolism, was significantly reduced in the intestine of the Nx group. Anti-inflammatory cytokine, interleukin 10, anti-bacterial peptide and cathelicidin-related antimicrobial peptide were also lowered in the Nx cohort. Butyrate treatment increased AMPK phosphorylation, improved renal function and controlled hyperglycemia.ConclusionsButyrate improves AMPK phosphorylation, increases GLP-1 secretion and promotes colonic mucin and TJ proteins, which strengthen the gut wall. This decreases LPS leakage and inflammation. Taken together, butyrate improves metabolic parameters such as insulin resistance and markers of renal failure in CKD animals.

Evaluation of Lineage Changes in the Gastric Mucosa Following Infection With Helicobacter pylori and Specified Intestinal Flora in INS-GAS Mice.

Gastric adenocarcinoma develops in metaplastic mucosa associated with Helicobacter pylori infection in the stomach. We have sought to evaluate the precise lineage changes in the stomachs of insulin-gastrin (INS-GAS) mice infected with H. pylori and/or intestinal flora (Altered Schaedler's Flora; ASF). Stomachs from groups infected with H. pylori contained progressive spasmolytic polypeptide-expressing metaplasia (SPEM) compared with germ-free and mice infected with ASF alone. The overall phenotype of the H. pylori-infected mice was dominated by Ulex europaeus lectin (UEAI)-positive foveolar hyperplasia that was distinct from GSII/CD44v9-positive SPEM. However, in the mice with H. pylori co-infected with ASF, we identified a subpopulation of UEAI-positive foveolar cells that co-expressed intestinal mucin 4 (MUC4). These regions of foveolar cells were variably positive for CD44v9 as well as TFF3. Interestingly, an intravascular lesion identified in a dual H. pylori/ASF-infected mouse expressed both UEAI and Muc4. Finally, we identified an increase in the number of tuft cells within the mucosa of H. pylori-infected groups. Our findings suggest that H. pylori infection promotes foveolar hyperplasia as well as metaplasia, while co-infection may promote progressive foveolar and metaplastic lesions as well as dysplasia. Grading of gastric lesions in mice as preneoplastic requires multiple immunostaining markers to assign lineage derivation and behavior.

Intestinal mucin activates human dendritic cells and IL-8 production in a glycan-specific manner

Cross-talk between different components of the intestinal barrier and the immune system may be important in maintaining gut homeostasis. A crucial part of the gut barrier is the mucus layer, a cross-linked gel on top of the intestinal epithelium that consists predominantly of the mucin glycoprotein MUC2. However, whether the mucin layer actively regulates intestinal immune cell responses is not clear. Because recent evidence suggests that intestinal dendritic cells (DCs) may be regulated by the mucus layer, we purified intestinal mucin, incubated it with human DCs, and determined the functional effects. Here we show that expression of the chemokine IL-8 and co-stimulatory DC markers CD86 and CD83 are significantly up-regulated on human DCs in the presence of intestinal mucins. Additionally, mucin-exposed DCs promoted neutrophil migration in an IL-8–dependent manner. The stimulatory effects of mucins on DCs were not due to mucin sample contaminants such as lipopolysaccharide, DNA, or contaminant proteins. Instead, mucin glycans are important for the pro-inflammatory effects on DCs. Thus, intestinal mucins are capable of inducing important pro-inflammatory functions in DCs, which could be important in driving inflammatory responses upon intestinal barrier damage.

Allium hookeri supplementation improves intestinal immune response against necrotic enteritis in young broiler chickens.

Three hundred birds (1 day old) were randomly assigned to 6 groups (n = 50 birds/treatment) and fed a basal diet (control) or basal diet supplemented with Allium hookeri (AH) root (1 or 3%). At day 14, half of the birds in each group were orally challenged with E. maxima 41A (1 × 104 cells/chicken), followed by C. perfringens infection (1 × 109 cfu/chicken) on day 18. Necrotic enteritis (NE)-associated infections and intestinal immune response were assessed by average body weight gain, lesion score, and oocyst shedding. The effect of dietary supplementation, AH, on transcript levels of pro-inflammatory cytokines, and tight junction proteins and mucin protein in the jejunum, were quantified by quantitative real-time (qRT)-PCR. At day 20, birds fed with diet supplementation (3% of AH) significantly weighted more than the control group. Although the NE-challenged had significantly reduced average body weight gain, there was no significance in the effect between diet × NE-challenge interactions on the average body weight gain. Among the NE-challenged groups, gut lesion score and oocyst shedding were significantly decreased in birds given AH (1 or 3%) compared to the control group. There was a correlation between diet and NE infection with regards to interleukin (IL)-17A, and inducible nitric oxide synthase (iNOS). The up-regulated transcript levels of cytokines IL-8, IL-17A, iNOS, and LITAF by NE challenged groups were significantly reduced by AH (1 or 3%) supplementation. Down-regulated expression levels of tight junction (TJ) proteins: junctional adhesion molecule 2 (JAM2), occluding, and intestinal mucin 2 (MUC2) by NE challenge, was up-regulated by the addition of AH (1 or 3%) supplementation. All TJ proteins (JAM2, ZO1, Ocluddin and MUC2) in the jejunum had a significant diet × NE-challenge interaction. These findings demonstrate that dietary supplementation of AH in chicken feed could be beneficially used to improve chicken health against NE.

A Sensitive and Rapid Method to Determin the Adhesion Capacity of Probiotics and Pathogenic Microorganisms to Human Gastrointestinal Mucins.

Mucus is the habitat for the microorganisms, bacteria and yeast that form the commensal flora. Mucins, the main macromolecules of mucus, and more specifically, the glycans that cover them, play essential roles in microbial gastrointestinal colonization. Probiotics and pathogens must also colonize mucus to have lasting positive or deleterious effects. The question of which mucin-harboured glycan motifs favour the adhesion of specific microorganisms remains very poorly studied. In the current study, a simple test based on the detection of fluorescent-labeled microorganisms raised against microgram amounts of mucins spotted on nitrocellulose was developed. The adhesion of various probiotic, commensal and pathogenic microorganisms was evaluated on a panel of human purified gastrointestinal mucins and compared with that of commercially available pig gastric mucins (PGM) and of mucins secreted by the colonic cancer cell line HT29-MTX. The latter two proved to be very poor indicators of adhesion capacity on intestinal mucins. Our results show that the nature of the sialylated cores of O-glycans, determined by MALDI MS-MS analysis, potentially enables sialic acid residues to modulate the adhesion of microorganisms either positively or negatively. Other identified factors affecting the adhesion propensity were O-glycan core types and the presence of blood group motifs. This test should help to select probiotics with enhanced adhesion capabilities as well as deciphering the role of specific mucin glycotopes on microbial adhesion.

Digestible threonine for slow-growing broilers: performance, carcass characteristics, intestinal mucin, and duodenal morphometry

ABSTRACT Five experiments were conducted to estimate the digestible threonine requirements of slow-growing broilers: experiment 1, starter phase (days 10 to 28); experiment 2, grower I phase (days 29 to 49); experiment 3, grower II phase (days 50 to 69); experiment 4, finisher phase (days 70 to 84); and experiment 5, which was specifically conducted to determine the production of intestinal mucin over two periods (days 50 to 69 and 70 to 84). Different birds were used in all experiments. [...]

Dietary supplementation of Allium hookeri improved intestinal immune response on necrotic enteritis of young broiler chickens

Abstract This study was conducted to evaluate the effects of dietary Allium hookeri on intestinal immune response of young broiler chickens induced with necrotic enteritis (NE). One hundred fifty birds (1 day old) were randomly assigned to 6 groups (n =25 birds/treatment) and fed a basal diet (control) or basal diet supplemented with Allium hookeri (AH) root at 1 or 3% of the basal diet; AH1 and AH3, respectively. Birds were orally challenged with E. maxima 41A (1 × 104 cells/chicken) on day14 and followed by C. perfringens infection (1 × 109 CFU/chicken) on day18. NE-associated infection and intestinal immune response were assessed by average body weight gain, lesion score and oocyst shedding. The effect of dietary supplementation with AH on transcript levels of pro-inflammatory cytokines, tight junction and mucin protein in the jejunum were quantified by qRT-PCR. At day 20, the birds fed 3 % of AH in diet (AH3) significantly weighted more than the control group though the NE-challenge significantly reduced average body weight gain compared to the uninfected control group. Among the NE-challenged groups, gut lesion score and oocyst shedding significantly decreased in the birds given with AH (1 or 3%) compared to the control group. Gene expression levels of pro-inflammatory cytokines IL-8, IL-17α, and LITAF decreased in AH3 groups compared to the infected control group though the levels significantly increased in the NE infected groups. Interestingly AH significantly increased transcript levels of intestinal tight junction proteins and mucin at 1% of diet, not 3% of diet. These results suggest that dietary supplementation of AH can improve chicken health by controling immune response against NE and it depends on the dietary level of AH.

Mucin gel assembly is controlled by a collective action of non-mucin proteins, disulfide bridges, Ca2+-mediated links, and hydrogen bonding

Mucus is characterized by multiple levels of assembly at different length scales which result in a unique set of rheological (flow) and mechanical properties. These physical properties determine its biological function as a highly selective barrier for transport of water and nutrients, while blocking penetration of pathogens and foreign particles. Altered integrity of the mucus layer in the small intestine has been associated with a number of gastrointestinal tract pathologies such as Crohn’s disease and cystic fibrosis. In this work, we uncover an intricate hierarchy of intestinal mucin (Muc2) assembly and show how complex rheological properties emerge from synergistic interactions between mucin glycoproteins, non-mucin proteins, and Ca2+. Using a novel method of mucus purification, we demonstrate the mechanism of assembly of Muc2 oligomers into viscoelastic microscale domains formed via hydrogen bonding and Ca2+-mediated links, which require the joint presence of Ca2+ ions and non-mucin proteins. These microscale domains aggregate to form a heterogeneous yield stress gel-like fluid, the macroscopic rheological properties of which are virtually identical to that of native intestinal mucus. Through proteomic analysis, we short-list potential protein candidates implicated in mucin assembly, thus paving the way for identifying the molecules responsible for the physiologically critical biophysical properties of mucus.

Study of mucin turnover in the small intestine by in vivo labeling

Mucins are highly glycosylated proteins which protect the epithelium. In the small intestine, the goblet cell-secreted Muc2 mucin constitutes the main component of the loose mucus layer that traps luminal material. The transmembrane mucin Muc17 forms part of the carbohydrate-rich glycocalyx covering intestinal epithelial cells. Our study aimed at investigating the turnover of these mucins in the small intestine by using in vivo labeling of O-glycans with N-azidoacetylgalactosamine. Mice were injected intraperitoneally and sacrificed every hour up to 12 hours and at 24 hours. Samples were fixed with preservation of the mucus layer and stained for Muc2 and Muc17. Turnover of Muc2 was slower in goblet cells of the crypts compared to goblet cells along the villi. Muc17 showed stable expression over time at the plasma membrane on villi tips, in crypts and at crypt openings. In conclusion, we have identified different subtypes of goblet cells based on their rate of mucin biosynthesis and secretion. In order to protect the intestinal epithelium from chemical and bacterial hazards, fast and frequent renewal of the secreted mucus layer in the villi area is combined with massive secretion of stored Muc2 from goblet cells in the upper crypt.

Brazilian green propolis hydroalcoholic extract reduces colon damages caused by dextran sulfate sodium-induced colitis in mice.

This study investigated the effects of Brazilian green propolis hydroalcoholic extract (BPE) in 3% w/v dextran sodium sulfate (DSS)-inducedcolitisin mice. The effects of BPE (3, 30 and 300mg/kg, p.o, by 7days) on the morphological (colon length and colon weight), clinical (disease activity index and weight loss), microscopic (histological score and mucin levels) and biochemical parameters were determined. The effects of BPE (300mg/kg, p.o) in the gastrointestinal transit of mice were also evaluated. As expected, the DSS ingestion damaged the colonic tissue, lowered the body weight, decreased the mucin levels, increased MPO activity,reduced SOD activity and GSH amount. In contrast, the treatment with BPE (300mg/kg) significantly reduced macroscopic colonic injury and the mucosal damage in colon on histopathological examination and reversed the decrease in mucin levels induced byDSS. It also significantly normalized the SOD activity and the levels of GSH, but did not elicit any effect on MPO activity in the colon. In addition, BPE did not change the gastric emptying or the intestinal transit rate of mice. Together, these results suggested that BPE reduced the signs of DSS-induced colitis in mice through maintenance of intestinal mucin barrier and favoring intestinal antioxidant defenses.

Quercetin Increases MUC2 and MUC5AC Gene Expression and Secretion in Intestinal Goblet Cell-Like LS174T via PLC/PKCα/ERK1-2 Pathway.

The main dietary flavonoid quercetin, is known to preserve the integrity of gastrointestinal barrier and to have anti-inflammatory, anti-cancer, anti-fibrotic, and other beneficial properties. Many of the biological effects of quercetin appear to be associated to the modulation of cell signaling pathways, rather than to its antioxidant activity. In spite of the large number of data available on the molecular and cellular mechanisms by which quercetin exerts its biological effects, including protection of intestinal barrier function, there is a lack of data about the role of this substance on the expression and/or the secretion of mucins released by intestinal goblet cells. Here we investigated the effects of quercetin on the secretion and the gene expression of the main intestinal gel-forming mucins, MUC2 and MUC5AC, and the signaling mechanisms underlined, in human intestinal goblet cell-like LS174T. We found that quercetin increases intracellular Ca2+ levels and induces MUC2 and MUC5AC secretion in a Ca2+-dependent manner. Quercetin also induces mRNA levels of both secretory mucins. Quercetin stimulation of LS174T cells increases phosphorylation levels of extracellular signal regulated kinase (ERK)1-2 and protein kinase C (PKC) α and the induction of MUC2 and MUC5AC secretion and mRNA relies on phospholipase C (PLC), PKC, and ERK1-2 signaling pathways since the PLC inhibitor U73122, the PKC inhibitor bisindolylmaleimide (BIM) and the ERK1-2 pathway inhibitor PD98059, all revert the stimulatory effects of quercetin. We also demonstrated that the induction of mucin gene expression by quercetin is not limited to goblet cells. Indeed, quercetin induces mRNA levels of MUC2 and MUC5AC via PKCα/ERK1-2 pathway also in the human intestinal epithelial Caco-2 cells. These data highlight a novel mechanism thereby quercetin, regulating the secretory function of intestinal goblet cells and mucin levels in enterocytes may exert its protective effects on intestinal mucosal barrier.

Smoking and the intestinal microbiome.

Studies are emerging alluding to the role of intestinal microbiome in the pathogenesis of diseases. Intestinal microbiome is susceptible to the influence of environmental factors such as smoking, and recent studies have indicated microbiome alterations in smokers. The aim of the study was to review the literature regarding the impact of smoking on the intestinal microbiome. A literature review of publications in PUBMED was performed using combinations of the terms "Intestinal/Gut/Gastrointestinal/Colonic" with "Microbiome/Microbiota/Microbial/Flora" and "Smoking/Smoker/Tobacco". We selected studies that were published between the years 2000 and 2016 as our inclusion criteria. Observational and interventional studies suggest that the composition of intestinal microbiome is altered due to smoking. In these studies, Proteobacteria and Bacteroidetes phyla were increased, as well as the genera of Clostridium, Bacteroides and Prevotella. On the other hand, Actinobacteria and Firmicutes phyla as well as the genera Bifidobacteria and Lactococcus were decreased. Smoking also decreased the diversity of the intestinal microbiome. Mechanisms that have been suggested to explain the effect of smoking on intestinal microbiome include: oxidative stress enhancement, alterations of intestinal tight junctions and intestinal mucin composition, and changes in acid-base balance. Interestingly, some smoking-induced alterations of intestinal microbiome resemble those demonstrated in conditions such as inflammatory bowel disease and obesity. Further studies should be performed to investigate this connection. Smoking has an effect on intestinal microbiome and is suggested to alter its composition. This interaction may contribute to the development of intestinal and systemic diseases, particularly inflammatory bowel diseases.

Characterization of the adult Aedes aegypti early midgut peritrophic matrix proteome using LC-MS.

The Aedes aegypti mosquito is the principal vector of arboviruses such as dengue, chikungunya, yellow fever, and Zika virus. These arboviruses are transmitted during adult female mosquito bloodfeeding. While these viruses must transverse the midgut to replicate, the blood meal must also reach the midgut to be digested, absorbed, or excreted, as aggregation of blood meal metabolites can be toxic to the female mosquito midgut. The midgut peritrophic matrix (PM), a semipermeable extracellular layer comprised of chitin fibrils, glycoproteins, and proteoglycans, is one such mechanism of protection for the mosquito midgut. However, this structure has not been characterized for adult female Ae. aegypti. We conducted a mass spectrometry based proteomic analysis to identify proteins that comprise or are associated with the adult female Ae. aegypti early midgut PM. Altogether, 474 unique proteins were identified, with 115 predicted as secreted. GO-term enrichment analysis revealed an abundance of serine-type proteases and several known and novel intestinal mucins. In addition, approximately 10% of the peptides identified corresponded to known salivary proteins, indicating Ae. aegypti mosquitoes extensively swallow their own salivary secretions. However, the physiological relevance of this remains unclear, and further studies are needed to determine PM proteins integral for midgut protection from blood meal derived toxicity and pathogen protection. Finally, we describe substantial discordance between previously described transcriptionally changes observed in the midgut in response to a bloodmeal and the presence of the corresponding protein in the PM. Data are available via ProteomeXchange with identifier PXD007627.

Intestinal Mucin Induces More Endocytosis but Less Transcytosis of Nanoparticles across Enterocytes by Triggering Nanoclustering and Strengthening the Retrograde Pathway.

Mucus, which is secreted by the goblet cells of enterocytes, constitutes the first obstacle encountered for the intestinal absorption of nanomedicines. For decades, mucus has simply been regarded as a physical barrier that hinders the permeation and absorption of drugs, because of its high viscosity and reticular structure, whereas the interaction of mucus ingredients with nanomedicines is usually neglected. It is unclear whether glycoproteins, as the main components of mucus, interact with nanomedicines. We also do not know how the potential interaction affects the subsequent transportation of nanomedicines through the intestinal epithelium. In this study, mucin as the key element of mucus was investigated to characterize the interaction of nanomedicines with mucus. PEG-modified gold nanoparticles (PGNPs) were fabricated as model nanoparticles. Mucin was found to adhere to the nanoparticle surface to form a corona structure and induce the clustering of PGNPs by joining particles together, demonstrating the interaction between mucin and PGNPs. In addition, two intestinal epithelia, Caco-2 (non- mucus secretion) and HT-29 (high mucus secretion), were compared to evaluate the influence of mucin on the cellular interaction of PGNPs. Amazingly, mucin altered the trafficking characteristic of PGNPs in intestinal epithelium. Both in vitro and in vivo investigations demonstrated more nanoparticles being internalized by cells due to the mucin coverage. However, mucin induced a significant reduction in the transcytosis of PGNPs across epithelial monolayers. The mechanism exploration further revealed that the "more endocytosis but less transcytosis (MELT)" effect was mainly attributed to the strengthened retrograde pathway in which more PGNPs were transported to Golgi apparatus and exocytosed back to the apical but not the basolateral side of the epithelial monolayers. The "MELT" effect endowed mucin with duality in the nanoparticle transportation. Therefore, the rational regulation based on the "MELT" effect will provide new insight into overcoming the mucus obstacle as a barrier and enhancing the oral absorption rate of nanomedicines.

Molecular basis for intestinal mucin recognition by galectin-3 and C-type lectins.

Intestinal mucins trigger immune responses upon recognition by dendritic cells via protein–carbohydrate interactions. We used a combination of structural, biochemical, biophysical, and cell-based approaches to decipher the specificity of the interaction between mucin glycans and mammalian lectins expressed in the gut, including galectin (Gal)-3 and C-type lectin receptors. Gal-3 differentially recognized intestinal mucins with different O-glycosylation profiles, as determined by mass spectrometry (MS). Modification of mucin glycosylation, via chemical treatment leading to a loss of terminal glycans, promoted the interaction of Gal-3 to poly-N-acetyllactosamine. Specific interactions were observed between mucins and mouse dendritic cell-associated lectin (mDectin)-2 or specific intercellular adhesion molecule–grabbing nonintegrin-related-1 (SIGN-R1), but not mDectin-1, using a cell-reporter assay, as also confirmed by atomic force spectroscopy. We characterized the N-glycosylation profile of mouse colonic mucin (Muc)-2 by MS and showed that the interaction with mDectin-2 was mediated by high-mannose N-glycans. Furthermore, we observed Gal-3 binding to the 3 C-type lectins by force spectroscopy. We showed that mDectin-1, mDectin-2, and SIGN-R1 are decorated by N-glycan structures that can be recognized by the carbohydrate recognition domain of Gal-3. These findings provide a structural basis for the role of mucins in mediating immune responses and new insights into the structure and function of major mammalian lectins.—Leclaire, C., Lecointe, K., Gunning, P. A., Tribolo, S., Kavanaugh, D. W., Wittmann, A., Latousakis, D., MacKenzie, D. A., Kawasaki, N., Juge, N. Molecular basis for intestinal mucin recognition by galectin-3 and C-type lectins.

Inhibition of MUC1 biosynthesis via threonyl-tRNA synthetase suppresses pancreatic cancer cell migration

Mucin1 (MUC1), a heterodimeric oncoprotein, containing tandem repeat structures with a high proportion of threonine, is aberrantly overexpressed in many human cancers including pancreatic cancer. Since the overall survival rate of pancreatic cancer patients has remained low for several decades, novel therapeutic approaches are highly needed. Intestinal mucin has been known to be affected by dietary threonine supply since de novo synthesis of mucin proteins is sensitive to luminal threonine concentration. However, it is unknown whether biosynthesis of MUC1 is regulated by threonine in human cancers. In this study, data provided suggests that threonine starvation reduces the level of MUC1 and inhibits the migration of MUC1-expressing pancreatic cancer cells. Interestingly, knockdown of threonyl-tRNA synthetase (TRS), an enzyme that catalyzes the ligation of threonine to its cognate tRNA, also suppresses MUC1 levels but not mRNA levels. The inhibitors of TRS decrease the level of MUC1 protein and prohibit the migration of MUC1-expressing pancreatic cancer cells. In addition, a positive correlation between TRS and MUC1 levels is observed in human pancreatic cancer cells. Concurrent with these results, the bioinformatics data indicate that co-expression of both TRS and MUC1 is correlated with the poor survival of pancreatic cancer patients. Taken together, these findings suggest a role for TRS in controlling MUC1-mediated cancer cell migration and provide insight into targeting TRS as a novel therapeutic approach to pancreatic cancer treatment.

Modulation of Intestinal Microbiota, Morphology and Mucin Composition by Dietary Insect Meal Inclusion in Free-Range Chickens

Modulation of Intestinal Microbiota, Morphology and Mucin Composition by Dietary Insect Meal Inclusion in Free-Range Chickens

Urachal adenocarcinoma - case report and literature review

Introduction. Urachal adenocarcinoma is extremely rare and comprises from 0.35% to 0.7% of all bladder tumors. The most common histologic subtype of urachal tumors is adenocarcinoma which can be associated with intestinal metaplasia and mucin production. Case report. We report a case of a 53-year-old patient who attented a urologist because of an intermittent haematuria lasting for three months. The ultrasound examination detected infiltration of the bladder at the fundus, 24 ? 29 mm in diameter. By the same wall, next to the tumor, there was an oval hypoechoic lesion about 40 mm in diameter. Computed tomography scan showed a solid, echogenic, strictly limited tumor at the fundus of the bladder, anteriorly, 32 ? 35 ? 22 mm in diameter which was positive after contrast application. The patient underwent partial cystectomy with complete excision of the tumor lesion 1.5 cm in healthy tissue. Histopathological analysis showed diagnosis of Adenocarcinoma mucinosum vesicae urinariae infiltrans. Patohistological findings detected a part of the urachal wall with a thin layer of fibromuscular tissue, chronic inflammation, microcalcifications in the lumen, flattened and desquamated epithelium. One year after the surgery, there were no signs of primary disease or metastases in other organs. Conclusion. Urachal adenocarcinoma is extremely rare. Long term survival could be achieved by surgical treatment in the early stage of the disease which consists of complete resection of urachal carcinoma and partial or total cystectomy.