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1.
Front Cell Infect Microbiol ; 14: 1391758, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38716194

RESUMO

Campylobacter jejuni, a Gram-negative bacterium, is one of the most common causes of foodborne illness worldwide. Its adhesion mechanism is mediated by several bacterial factors, including flagellum, protein adhesins, lipooligosaccharides, proteases, and host factors, such as surface glycans on epithelial cells and mucins. Fungal lectins, specialized carbohydrate-binding proteins, can bind to specific glycans on host and bacterial cells and thus influence pathogenesis. In this study, we investigated the effects of fungal lectins and protease inhibitors on the adhesion of C. jejuni to model biotic surfaces (mucin, fibronectin, and collagen) and Caco-2 cells as well as the invasion of Caco-2 cells. The lectins Marasmius oreades agglutinin (MOA) and Laccaria bicolor tectonin 2 (Tec2) showed remarkable efficacy in all experiments. In addition, different pre-incubations of lectins with C. jejuni or Caco-2 cells significantly inhibited the ability of C. jejuni to adhere to and invade Caco-2 cells, but to varying degrees. Pre-incubation of Caco-2 cells with selected lectins reduced the number of invasive C. jejuni cells the most, while simultaneous incubation showed the greatest reduction in adherent C. jejuni cells. These results suggest that fungal lectins are a promising tool for the prevention and treatment of C. jejuni infections. Furthermore, this study highlights the potential of fungi as a rich reservoir for novel anti-adhesive agents.


Assuntos
Aderência Bacteriana , Campylobacter jejuni , Lectinas , Inibidores de Proteases , Campylobacter jejuni/efeitos dos fármacos , Campylobacter jejuni/fisiologia , Campylobacter jejuni/metabolismo , Humanos , Células CACO-2 , Aderência Bacteriana/efeitos dos fármacos , Lectinas/metabolismo , Lectinas/farmacologia , Inibidores de Proteases/farmacologia , Inibidores de Proteases/metabolismo , Fungos/efeitos dos fármacos , Mucinas/metabolismo , Células Epiteliais/microbiologia , Fibronectinas/metabolismo
2.
Sheng Wu Gong Cheng Xue Bao ; 40(5): 1498-1508, 2024 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-38783811

RESUMO

To investigate the role of recombinant mussel mucin in wound healing, we aimed to prepare this mucin using Pichia pastoris as the host microbe. Our method involved constructing a genetically engineered strain of P. pastoris that expressed a fusion protein consisting of Mfp-3 and preCol-P peptide segments of mussel. After fermentation and purification, we obtained a pure recombinant mussel mucin product. We then conducted experiments to evaluate its effect at both the cellular and animal levels. At the cellular level, we examined its impact on the proliferation and migration of mouse fibroblast L929. At the animal level, we assessed its ability to promote wound healing after full-layer skin resection in rats. Our results showed that the recombinant mussel mucin protein has a content of 90.28% and a purity of 96.49%. The content of 3,4-dihydroxyphenylalanine (DOPA) was 0.73 wt%, and the endotoxin content was less than 0.5 EU/mg. Importantly, the recombinant mussel mucin protein significantly promoted both the migration and proliferation of mouse fibroblast, as well as the wound healing in rat skin. In conclusion, our findings demonstrate that recombinant mussel mucin has the potential to promote wound healing and can be considered a promising medical biomaterial.


Assuntos
Cicatrização , Animais , Cicatrização/efeitos dos fármacos , Ratos , Camundongos , Mucinas/metabolismo , Mucinas/genética , Bivalves , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/genética , Proteínas Recombinantes/farmacologia , Fibroblastos/metabolismo , Fibroblastos/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/biossíntese , Proteínas Recombinantes de Fusão/farmacologia , Masculino , Ratos Sprague-Dawley , Saccharomycetales
3.
Food Res Int ; 183: 114185, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38760122

RESUMO

Low- and no-calorie sweeteners reduce the amount of carbohydrates in foods and beverages. However, concerns about taste perception surrounding the role of non-nutritive sweeteners in the oral cavity remain unanswered. One of the parameters that influences taste perception is the diffusion coefficient of the sweetener molecules inside the mucin layer lining the mouth. This study investigated the impact of diffusion coefficients of common high-intensity sweeteners on taste perception focusing on the sweeteners' diffusion through mucin. Transwell Permeable Support well plates were used to measure diffusion coefficients of samples that were collected at specific intervals to estimate the coefficients based on concentration measurements. The diffusion coefficients of acesulfame-K, aspartame, rebaudioside M, sucralose, and sucrose with and without NaCl were compared. We found that different sweeteners show different diffusion behavior through mucin and that the presence of salt enhances the diffusion. These findings contribute insights into the diffusion of high-intensity sweeteners, offer a way to evaluate diffusion coefficients in real-time, and inform the development of products with improved taste profiles.


Assuntos
Mucinas , Sacarose , Edulcorantes , Difusão , Mucinas/metabolismo , Sacarose/análogos & derivados , Percepção Gustatória , Humanos , Tiazinas
4.
Nat Microbiol ; 9(5): 1176-1188, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38684911

RESUMO

Matching donor and recipient blood groups based on red blood cell (RBC) surface ABO glycans and antibodies in plasma is crucial to avoid potentially fatal reactions during transfusions. Enzymatic conversion of RBC glycans to the universal group O is an attractive solution to simplify blood logistics and prevent ABO-mismatched transfusions. The gut symbiont Akkermansia muciniphila can degrade mucin O-glycans including ABO epitopes. Here we biochemically evaluated 23 Akkermansia glycosyl hydrolases and identified exoglycosidase combinations which efficiently transformed both A and B antigens and four of their carbohydrate extensions. Enzymatic removal of canonical and extended ABO antigens on RBCs significantly improved compatibility with group O plasmas, compared to conversion of A or B antigens alone. Finally, structural analyses of two B-converting enzymes identified a previously unknown putative carbohydrate-binding module. This study demonstrates the potential utility of mucin-degrading gut bacteria as valuable sources of enzymes for production of universal blood for transfusions.


Assuntos
Sistema ABO de Grupos Sanguíneos , Akkermansia , Glicosídeo Hidrolases , Sistema ABO de Grupos Sanguíneos/imunologia , Humanos , Glicosídeo Hidrolases/metabolismo , Mucinas/metabolismo , Eritrócitos/imunologia , Polissacarídeos/metabolismo , Microbioma Gastrointestinal , Antígenos de Grupos Sanguíneos/metabolismo , Antígenos de Grupos Sanguíneos/imunologia , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/imunologia
5.
mSystems ; 9(5): e0024624, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38564708

RESUMO

Dietary fiber deprivation is linked to probiotic extinction, mucus barrier dysbiosis, and the overgrowth of mucin-degrading bacteria. However, whether and how mucin could rescue fiber deprivation-induced intestinal barrier defects remains largely unexplored. Here, we sought to investigate the potential role and mechanism by which exogenous mucin maintains the gut barrier function. The results showed that dietary mucin alleviated fiber deprivation-induced disruption of colonic barrier integrity and reduced spermine production in vivo. Importantly, we highlighted that microbial-derived spermine production, but not host-produced spermine, increased significantly after mucin supplementation, with a positive association with upgraded colonic Lactobacillus abundance. After employing an in vitro model, the microbial-derived spermine was consistently dominated by both mucin and Lactobacillus spp. Furthermore, Limosilactobacillus mucosae was identified as an essential spermine-producing Lactobacillus spp., and this isolated strain was responsible for spermine accumulation, especially after adhering to mucin in vitro. Specifically, the mucin-supplemented bacterial supernatant of Limosilactobacillus mucosae was verified to promote intestinal barrier functions through the increased spermine production with a dependence on enhanced arginine metabolism. Overall, these findings collectively provide evidence that mucin-modulated microbial arginine metabolism bridged the interplay between microbes and gut barrier function, illustrating possible implications for host gut health. IMPORTANCE: Microbial metabolites like short-chain fatty acids produced by dietary fiber fermentation have been demonstrated to have beneficial effects on intestinal health. However, it is essential to acknowledge that certain amino acids entering the colon can be metabolized by microorganisms to produce polyamines. The polyamines can promote the renewal of intestinal epithelial cell and maintain host-microbe homeostasis. Our study highlighted the specific enrichment by mucin on promoting the arginine metabolism in Limosilactobacillus mucosae to produce spermine, suggesting that microbial-derived polyamines support a significant enhancement on the goblet cell proliferation and barrier function.


Assuntos
Arginina , Colo , Microbioma Gastrointestinal , Mucosa Intestinal , Mucinas , Espermina , Espermina/metabolismo , Mucinas/metabolismo , Arginina/metabolismo , Arginina/farmacologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Animais , Microbioma Gastrointestinal/fisiologia , Colo/microbiologia , Colo/metabolismo , Masculino , Camundongos , Lactobacillus/metabolismo , Humanos , Fibras na Dieta/metabolismo , Camundongos Endogâmicos C57BL
6.
Food Res Int ; 184: 114246, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38609225

RESUMO

Food-derived mucins are glycoproteins rich in sialic acid, but their digestive properties and potential health benefits for humans have been scarcely investigated. In this work, ovomucin (OVM, rich in N-acetylneuraminic acid, about 3 %), porcine small intestinal mucin (PSIM, rich in N-glycolylneuraminic acid, about 1 %), the desialylated OVM (AOVM) and the desialylated PSIM (APSIM) were selected to examine their digestion and their impact on the gut microbiota of elderly individuals. The results shown that, the proportion of low-molecular-weight proteins increased after simulated digestion of these four mucins, with concomitant comparable antioxidant activity observed. Desialylation markedly increased the degradation and digestion rate of mucins. In vitro fecal fermentation was conducted with these mucins using fecal samples from individuals of different age groups: young, low-age and high-age elderly. Fecal fermentation with mucin digestive solution stimulated the production of organic acids in the group with fecal sample of the elderly individuals. Among them, the OVM group demonstrated the most favorable outcomes. The OVM and APSIM groups elevated the relative abundance of beneficial bacteria such as Lactobacillus and Bifidobacterium, while diminishing the presence of pathogenic bacteria such as Klebsiella. Conversely, the probiotic effects of AOVM and PSIM were attenuated or even exhibited adverse effects. Hence, mucins originating from different sources and possessing distinct glycosylation patterns exhibit diverse biological functions. Our findings can offer valuable insights for developing a well-balanced and nutritious diet tailored to the elderly population.


Assuntos
Microbioma Gastrointestinal , Mucinas , Humanos , Idoso , Animais , Suínos , Dieta , Alimentos , Bifidobacterium
7.
J Theor Biol ; 587: 111824, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38604595

RESUMO

The human gut microbiota relies on complex carbohydrates (glycans) for energy and growth, primarily dietary fiber and host-derived mucins. We introduce a mathematical model of a glycan generalist and a mucin specialist in a two-compartment chemostat model of the human colon. Our objective is to characterize the influence of dietary fiber and mucin supply on the abundance of mucin-degrading species within the gut ecosystem. Current mathematical gut reactor models that include the enzymatic degradation of glycans do not differentiate between glycan types and their degraders. The model we present distinguishes between a generalist that can degrade both dietary fiber and mucin, and a specialist species that can only degrade mucin. The integrity of the colonic mucus barrier is essential for overall human health and well-being, with the mucin specialist Akkermanisa muciniphila being associated with a healthy mucus layer. Competition, particularly between the specialist and generalists like Bacteroides thetaiotaomicron, may lead to mucus layer erosion, especially during periods of dietary fiber deprivation. Our model treats the colon as a gut reactor system, dividing it into two compartments that represent the lumen and the mucus of the gut, resulting in a complex system of ordinary differential equations with a large and uncertain parameter space. To understand the influence of model parameters on long-term behavior, we employ a random forest classifier, a supervised machine learning method. Additionally, a variance-based sensitivity analysis is utilized to determine the sensitivity of steady-state values to changes in model parameter inputs. By constructing this model, we can investigate the underlying mechanisms that control gut microbiota composition and function, free from confounding factors.


Assuntos
Fibras na Dieta , Microbioma Gastrointestinal , Modelos Biológicos , Mucinas , Muco , Mucinas/metabolismo , Fibras na Dieta/metabolismo , Humanos , Microbioma Gastrointestinal/fisiologia , Muco/metabolismo , Colo/metabolismo , Colo/microbiologia , Polissacarídeos/metabolismo
8.
J Phys Chem A ; 128(15): 3015-3023, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38593044

RESUMO

Respiratory viruses, such as influenza and severe acute respiratory syndrome coronavirus 2, represent a substantial public health burden and are largely transmitted through respiratory droplets and aerosols. Environmental factors such as relative humidity (RH) and temperature impact virus transmission rates, and a precise mechanistic understanding of the connection between these environmental factors and virus transmission would improve efforts to mitigate respiratory disease transmission. Previous studies on supermicrometer particles observed RH-dependent phase transitions and linked particle phase state to virus viability. Phase transitions in atmospheric aerosols are dependent on size in the submicrometer range, and actual respiratory particles are expelled over a large size range, including submicrometer aerosols that can transmit diseases over long distances. Here, we directly investigated the phase transitions of submicrometer model respiratory aerosols. A probe molecule, Nile red, was added to particle systems including multiple mucin/salt mixtures, a growth medium, and simulated lung fluid. For each system, the polarity-dependent fluorescence emission was measured following RH conditioning. Notably, the fluorescence measurements of mucin/NaCl and Dulbecco's modified Eagle's medium particles indicated that liquid-liquid phase separation (LLPS) also occurs in submicron particles, suggesting that LLPS can also impact the viability of viruses in submicron particles and thus affect aerosol virus transmission. Furthermore, the utility of fluorescence-based measurements to study submicrometer respiratory particle physicochemical properties in situ is demonstrated.


Assuntos
Mucinas , Aerossóis e Gotículas Respiratórios , Umidade , Aerossóis/química
9.
Nutrients ; 16(7)2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38612988

RESUMO

The goblet cells of the gastrointestinal tract (GIT) produce glycoproteins called mucins that form a protective barrier from digestive contents and external stimuli. Recent evidence suggests that the milk fat globule membrane (MFGM) and its milk phospholipid component (MPL) can benefit the GIT through improving barrier function. Our objective was to compare the effects of two digested MFGM ingredients with or without dextran sodium sulfate (DSS)-induced barrier stress on mucin proteins. Co-cultured Caco-2/HT29-MTX intestinal cells were treated with in vitro digests of 2%, 5%, and 10% (w/v) MFGM or MPL alone for 6 h or followed by challenge with 2.5% DSS (6 h). Transepithelial electrical resistance and fluorescein isothiocyanate (FITC)-dextran (FD4) permeability measurements were used to measure changes in barrier integrity. Mucin characterization was performed using a combination of slot blotting techniques for secreted (MUC5AC, MUC2) and transmembrane (MUC3A, MUC1) mucins, scanning electron microscopy (SEM), and periodic acid Schiff (PAS)/Alcian blue staining. Digested MFGM and MPL prevented a DSS-induced reduction in secreted mucins, which corresponded to the prevention of DSS-induced increases in FD4 permeability. SEM and PAS/Alcian blue staining showed similar visual trends for secreted mucin production. A predictive bioinformatic approach was also used to identify potential KEGG pathways involved in MFGM-mediated mucosal maintenance under colitis conditions. This preliminary in silico evidence, combined with our in vitro findings, suggests the role of MFGM in inducing repair and maintenance of the mucosal barrier.


Assuntos
Dextranos , Fluoresceína-5-Isotiocianato/análogos & derivados , Glicolipídeos , Glicoproteínas , Gotículas Lipídicas , Humanos , Células CACO-2 , Azul Alciano , Glicoproteínas/farmacologia , Células Epiteliais , Mucinas
10.
Zhonghua Bing Li Xue Za Zhi ; 53(4): 351-357, 2024 Apr 08.
Artigo em Chinês | MEDLINE | ID: mdl-38556818

RESUMO

Objective: To investigate the clinicopathological and molecular genetic characteristics of Crohn's disease (CD). Methods: A retrospective analysis was conducted on 52 CD patients who underwent surgical resection at the First Affiliated Hospital of Nanjing Medical University between January 2014 and June 2023. Clinical presentations and histopathological features were assessed. Whole-genome sequencing was performed on 17 of the samples, followed by sequencing and pathway enrichment analyses. Immunohistochemistry was used to assess the expression of frequently mutated genes. Results: Among the 52 patients, 34 were males and 18 were females, male-to-female ratio was 1.9∶1.0, with a median age of 45 years at surgery and 35 years at diagnosis. According to the Montreal classification, A3 (51.9%,27/52), B2 (61.5%, 32/52), and L3 (50.0%,26/52) subtypes were the most predominant. Abdominal pain and diarrhea were the common symptoms. Histopathological features seen in all 52 patients included transmural inflammation, disruption of cryptal architecture, lymphoplasmacytic infiltration, varying degrees of submucosal fibrosis and thickening, increased enteric nerve fibers and neuronal proliferation. Mucosal defects, fissure ulcers, abscesses, pseudopolyps, and adenomatous proliferation were also observed in 51 (98.1%), 38 (73.1%), 28 (53.8%), 45 (86.5%), and 28 (53.8%) cases, respectively. Thirty-one (59.6%) cases had non-caseating granulomas, and 3 (5.8%) cases had intestinal mucosal glandular epithelial dysplasia. Molecular analysis showed that 12/17 CD patients exhibited mutations in at least one mucin family gene (MUC2, MUC3A, MUC4, MUC6, MUC12, MUC17), and MUC4 was the most frequently mutated in 7/17 of cases. Immunohistochemical stains showed reduced MUC4 expression in epithelial cells, with increased MUC4 expression in the epithelial surface, particularly around areas of inflammatory cell aggregation; and minimal expression in the lower half of the epithelium. Conclusions: CD exhibits diverse clinical and pathological features, necessitating a comprehensive multidimensional analysis for diagnosis. Mutations and expression alterations in mucin family genes, particularly MUC4, may play crucial roles in the pathogenesis of CD.


Assuntos
Doença de Crohn , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Doença de Crohn/genética , Doença de Crohn/diagnóstico , Doença de Crohn/patologia , Estudos Retrospectivos , Mucinas , Células Epiteliais/patologia , Biologia Molecular
11.
Vet Q ; 44(1): 1-18, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38606662

RESUMO

Complex respiratory diseases are a significant challenge for the livestock industry worldwide. These diseases considerably impact animal health and welfare and cause severe economic losses. One of the first lines of pathogen defense combines the respiratory tract mucus, a highly viscous material primarily composed of mucins, and a thriving multi-kingdom microbial ecosystem. The microbiome-mucin interplay protects from unwanted substances and organisms, but its dysfunction may enable pathogenic infections and the onset of respiratory disease. Emerging evidence also shows that noncoding regulatory RNAs might modulate the structure and function of the microbiome-mucin relationship. This opinion paper unearths the current understanding of the triangular relationship between mucins, the microbiome, and noncoding RNAs in the context of respiratory infections in animals of veterinary interest. There is a need to look at these molecular underpinnings that dictate distinct health and disease outcomes to implement effective prevention, surveillance, and timely intervention strategies tailored to the different epidemiological contexts.


Assuntos
Microbiota , Doenças Respiratórias , Animais , Mucinas/química , Gado , Doenças Respiratórias/veterinária
12.
Future Microbiol ; 19: 335-347, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38470403

RESUMO

Aim: This study aimed to examine the impact of fecal water (FW) of active and remissive Crohn's disease (CD) patients on mucin degradation and epithelial barrier function. Methods: FW and bacterial membrane vesicles (MVs) were isolated from fresh fecal samples of six healthy controls (HCs) and 12 CD patients. Bacterial composition was determined by 16S rRNA gene amplicon sequencing. Results: In vitro FW-induced mucin degradation was higher in CD samples versus HC (p < 0.01), but not associated with specific bacterial genera. FW of three remissive samples decreased transepithelial electrical resistance in Caco-2 cells by 78-87% (p < 0.001). MVs did not induce barrier alterations. Conclusion: The higher mucin-degradation capacity of CD-derived FW might suggest contributions of microbial products to CD pathophysiology.


Assuntos
Doença de Crohn , Humanos , Doença de Crohn/microbiologia , Mucinas/metabolismo , Células CACO-2 , RNA Ribossômico 16S/genética , Mucosa Intestinal/metabolismo , Permeabilidade
13.
Biomaterials ; 308: 122541, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38547832

RESUMO

Herein, we describe the 3'-sialyllactose-polyethyleneimine-chlorine e6 conjugate (3PC), meticulously engineered to effectively target Helicobacter bacteria (H. pylori) within the gastric environment. The composition of 3PC comprises polyethyleneimine, a cationic polymer, 3'-sialyllactose, which exhibits a specific binding affinity for H. pylori surface proteins, and a photosensitizer capable of generating oxygen radicals in response to specific wavelengths. The distinctive feature of 3PC lies in its capacity to enhance interaction with the anionic mucus layer facilitated by electrostatic forces. This interaction results in prolonged residence within the intestinal environment. The extended vacation in the intestinal milieu overcomes inherent limitations that have historically impeded conventional antibiotics from efficiently reaching and targeting H. pylori. 3PC can be harnessed as a potent tool for antibacterial photodynamic therapy, and its versatility extends to addressing the challenges posed by various antibiotic-resistant strains. The exceptional efficacy of 3PC in enhancing intestinal residence time and eradicating H. pylori has been robustly substantiated in animal models, particularly in mice. In summary, 3PC is a formidable agent capable of eradicating H. pylori, irrespective of its antibiotic resistance status, by efficiently penetrating and selectively targeting the mucus layer within the gastric environment.


Assuntos
Antibacterianos , Infecções por Helicobacter , Helicobacter pylori , Mucinas , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/genética , Animais , Antibacterianos/farmacologia , Antibacterianos/química , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/microbiologia , Mucinas/metabolismo , Mucinas/química , Farmacorresistência Bacteriana/efeitos dos fármacos , Farmacorresistência Bacteriana/genética , Mutação , Camundongos , Fotoquimioterapia/métodos , Polímeros/química , Humanos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/uso terapêutico , Adesivos/química , Adesivos/farmacologia
14.
J Nucl Med ; 65(4): 580-585, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38485271

RESUMO

Aberrantly expressed glycans on mucins such as mucin-16 (MUC16) are implicated in the biology that promotes ovarian cancer (OC) malignancy. Here, we investigated the theranostic potential of a humanized antibody, huAR9.6, targeting fully glycosylated and hypoglycosylated MUC16 isoforms. Methods: In vitro and in vivo targeting of the diagnostic radiotracer [89Zr]Zr-DFO-huAR9.6 was investigated via binding experiments, immuno-PET imaging, and biodistribution studies on OC mouse models. Ovarian xenografts were used to determine the safety and efficacy of the therapeutic version, [177Lu]Lu-CHX-A″-DTPA-huAR9.6. Results: In vivo uptake of [89Zr]Zr-DFO-huAR9.6 supported in vitro-determined expression levels: high uptake in OVCAR3 and OVCAR4 tumors, low uptake in OVCAR5 tumors, and no uptake in OVCAR8 tumors. Accordingly, [177Lu]Lu-CHX-A″-DTPA-huAR9.6 displayed strong antitumor effects in the OVCAR3 model and improved overall survival in the OVCAR3 and OVCAR5 models in comparison to the saline control. Hematologic toxicity was transient in both models. Conclusion: PET imaging of OC xenografts showed that [89Zr]Zr-DFO-huAR9.6 delineated MUC16 expression levels, which correlated with in vitro results. Additionally, we showed that [177Lu]Lu-CHX-A″-DTPA-huAR9.6 displayed strong antitumor effects in highly MUC16-expressing tumors. These findings demonstrate great potential for 89Zr- and 177Lu-labeled huAR9.6 as theranostic tools for the diagnosis and treatment of OC.


Assuntos
Anticorpos Monoclonais Humanizados , Antígeno Ca-125 , Mucinas , Neoplasias Ovarianas , Animais , Feminino , Humanos , Camundongos , Apoptose , Antígeno Ca-125/imunologia , Linhagem Celular Tumoral , Proteínas de Membrana/imunologia , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/terapia , Ácido Pentético , Medicina de Precisão , Distribuição Tecidual , Anticorpos Monoclonais Humanizados/uso terapêutico , Mucinas/imunologia
15.
Nat Commun ; 15(1): 2611, 2024 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-38521783

RESUMO

The dense O-glycosylation of mucins plays an important role in the defensive properties of the mucus hydrogel. Aberrant glycosylation is often correlated with inflammation and pathology such as COPD, cancer, and Crohn's disease. The inherent complexity of glycans and the diversity in the O-core structure constitute fundamental challenges for the analysis of mucin-type O-glycans. Due to coexistence of multiple isomers, multidimensional workflows such as LC-MS are required. To separate the highly polar carbohydrates, porous graphitized carbon is often used as a stationary phase. However, LC-MS workflows are time-consuming and lack reproducibility. Here we present a rapid alternative for separating and identifying O-glycans released from mucins based on trapped ion mobility mass spectrometry. Compared to established LC-MS, the acquisition time is reduced from an hour to two minutes. To test the validity, the developed workflow was applied to sputum samples from cystic fibrosis patients to map O-glycosylation features associated with disease.


Assuntos
Mucinas , Espectrometria de Massas em Tandem , Humanos , Mucinas/metabolismo , Espectrometria de Massas em Tandem/métodos , Reprodutibilidade dos Testes , Polissacarídeos/química , Glicosilação
16.
Sci Rep ; 14(1): 6954, 2024 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-38521809

RESUMO

Mucin protein glycosylation is important in determining biological properties of mucus gels, which form protective barriers at mucosal surfaces of the body such as the intestine. Ecological factors including: age, sex, and diet can change mucus barrier properties by modulating mucin glycosylation. However, as our understanding stems from controlled laboratory studies in house mice, the combined influence of ecological factors on mucin glycosylation in real-world contexts remains limited. In this study, we used histological staining with 'Alcian Blue, Periodic Acid, Schiff's' and 'High-Iron diamine' to assess the acidic nature of mucins stored within goblet cells of the intestine, in a wild mouse population (Mus musculus). Using statistical models, we identified sex as among the most influential ecological factors determining the acidity of intestinal mucin glycans in wild mice. Our data from wild mice and experiments using laboratory mice suggest estrogen signalling associates with an increase in the relative abundance of sialylated mucins. Thus, estrogen signalling may underpin sex differences observed in the colonic mucus of wild and laboratory mice. These findings highlight the significant influence of ecological parameters on mucosal barrier sites and the complementary role of wild populations in augmenting standard laboratory studies in the advancement of mucus biology.


Assuntos
Colo , Mucinas , Camundongos , Feminino , Masculino , Animais , Mucinas/metabolismo , Colo/patologia , Células Caliciformes/metabolismo , Intestinos , Estrogênios/metabolismo , Mucina-2/metabolismo , Mucosa Intestinal/metabolismo
17.
Biomolecules ; 14(3)2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38540735

RESUMO

Mucins are a family of high-molecular-weight glycoproteins. MUC1 is widely studied for its role in distinct types of cancers. In many human epithelial malignancies, MUC1 is frequently overexpressed, and its intracellular activities are crucial for cell biology. MUC1 overexpression can enhance cancer cell proliferation by modulating cell metabolism. When epithelial cells lose their tight connections, due to the loss of polarity, the mucins become dispersed on both sides of the epithelial membrane, leading to an abnormal mucin interactome with the membrane. Tumor-related MUC1 exhibits certain features, such as loss of apical localization and aberrant glycosylation that might cause the formation of tumor-related antigen epitopes. Renal cell carcinoma (RCC) accounts for approximately 3% of adult malignancies and it is the most common kidney cancer. The exact role of MUC1 in this tumor is unknown. Evidence suggests that it may play a role in several oncogenic pathways, including proliferation, metabolic reprogramming, chemoresistance, and angiogenesis. The purpose of this review is to explore the role of MUC1 and the meaning of its overexpression in epithelial tumors and in particular in RCC.


Assuntos
Carcinoma de Células Renais , Carcinoma , Neoplasias Renais , Adulto , Humanos , Carcinoma de Células Renais/genética , Mucina-1/genética , Mucinas , Antígenos de Neoplasias
18.
J Appl Microbiol ; 135(4)2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38544331

RESUMO

AIMS: Indole and mucin are compounds found in the host environment as they are produced by the host or by the host-associated microbiota. This study investigated whether indole and mucin impact Clostridium perfringens growth and sporulation, as well as enterotoxin production and biofilm formation. METHODS AND RESULTS: There was no impact on growth of Cl. perfringens for up to 400 µM indole and 240 mg/l mucin, and neither indole nor mucin affected sporulation. Reverse-transcriptase qPCR showed that mucin strongly upregulated the expression of Cl. perfringens enterotoxin (up to 121-fold increase), whereas indole had a much more modest effect (2-fold). This was also reflected in increased Cl. perfringens enterotoxin levels in mucin-treated Cl. perfringens (as assessed by a reversed passive latex agglutination assay). Finally, mucin and indole significantly increased biofilm formation of Cl. perfringens, although the effect size was relatively small (less than 1.5 fold). CONCLUSION: These results indicate that Cl. perfringens can sense its presence in a host environment by responding to mucin, and thereby markedly increased enterotoxin production.


Assuntos
Clostridium perfringens , Enterotoxinas , Clostridium perfringens/genética , Enterotoxinas/genética , Mucinas/metabolismo , Esporos Bacterianos , Biofilmes
19.
Anal Chem ; 96(13): 5242-5250, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38512228

RESUMO

Mucin-domain glycoproteins are densely O-glycosylated and play critical roles in a host of healthy and disease-driven biological functions. Previously, we developed a mucin-selective enrichment strategy by employing a catalytically inactive mucinase (StcE) conjugated to a solid support. While this method was effective, it suffered from low throughput and high sample requirements. Further, the elution step required boiling in SDS, thus necessitating an in-gel digest with trypsin. Here, we introduce innovative elution conditions amenable to mucinase digestion and downstream analysis using mass spectrometry. This increased throughput and lowered sample input while maintaining mucin selectivity and enhancing the glycopeptide signal. We then benchmarked this technique against different O-glycan binding moieties for their ability to enrich mucins from various cell lines and human serum. Overall, the new method outperformed our previous procedure and all of the other enrichment techniques tested. This allowed for the effective isolation of more mucin-domain glycoproteins, resulting in a high number of O-glycopeptides, thus enhancing our ability to analyze the mucinome.


Assuntos
Glicoproteínas , Mucinas , Humanos , Mucinas/química , Espectrometria de Massas , Glicosilação , Glicopeptídeos/química
20.
J Cosmet Dermatol ; 23(4): 1113-1121, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38429932

RESUMO

BACKGROUND: Snail mucin is becoming increasingly popular for its wide range of ingredients and potential benefits. Snail extract's widespread appearance in cosmetic formulations encourages an investigation into the medical and cosmetic benefits. AIMS: This study aims to explore current literature on the variety of snail mucin applications. Specifically, we present a review of the uses, global market estimates and projects, and limitations to snail mucin. METHODS: A literature search was conducted on PubMed reviewing snail mucin and their application in medical and dermatologic fields examining their uses. Economic reports were also investigated for Global Market estimates. RESULTS: The therapeutic use of snail mucin in medical fields has been studied as antimicrobial agents, drug delivery vehicles, antitumor agents, wound healing agents, and biomaterial coatings among others. Additionally, the use in cosmetic fields includes antiaging, hydrating, anti-acne, scarring, and hyperpigmentation treatments. It is important to highlight that most studies conducted were preclinical or small clinical studies, stressing the need for additional large-scale clinical trials to support these claims. Investigations into the global market found estimates ranging from $457 million to $1.2 billion with upward projections in the upcoming decade. Limitations include ethical habitats for collection, allergy investigation, and missing clinical studies. CONCLUSIONS: The findings presented here emphasize the expanding uses of snail mucin and its ingredients alongside a growing market cosmetic industry should consider. We also emphasize the need for appropriate clinical trials into the stated benefits of snail mucin to ensure consumer safety and ethical extraction of mucin.


Assuntos
Cosméticos , Mucinas , Pele , Humanos , Produtos Biológicos/química , Produtos Biológicos/uso terapêutico , Cicatriz/tratamento farmacológico , Cosméticos/química , Mucinas/uso terapêutico , Pele/efeitos dos fármacos , Caramujos/química
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