-
Investigative Ophthalmology & Visual... Jun 2024This study aimed to explore protective effects and potential mechanism of ectoine, a natural osmoprotectant, on ocular surface mucin production in dry eye disease.
PURPOSE
This study aimed to explore protective effects and potential mechanism of ectoine, a natural osmoprotectant, on ocular surface mucin production in dry eye disease.
METHODS
A dry eye model was established in C57BL/6 mice exposed to desiccating stress (DS) with untreated (UT) mice as controls. DS mice were topically treated with 2.0% ectoine or PBS vehicle. Corneal epithelial defects were assessed by Oregon Green Dextran (OGD) fluorescent staining. Conjunctival goblet cells, ocular mucins, and T help (Th) cytokines were evaluated by immunofluorescent staining or ELISA, and RT-qPCR.
RESULTS
Compared with UT mice, corneal epithelial defects were detected as strong punctate OGD fluorescent staining in DS mice with vehicle, whereas ectoine treatment largely reduced OGD staining to near-normal levels. Conjunctival goblet cell density and cell size decreased markedly in DS mice, but was significantly recovered by ectoine treatment. The protein production and mRNA expression of two gel-forming secreted MUC5AC and MUC2, and 4 transmembrane mucins, MUC1, MUC4, MUC16, and MUC15, largely decreased in DS mice, but was restored by ectoine. Furthermore, Th2 cytokine IL-13 was inhibited, whereas Th1 cytokine IFN-γ was stimulated at protein and mRNA levels in conjunctiva and draining cervical lymph nodes (CLNs) of DS mice, leading to decreased IL-13/IFN-γ ratio. Interestingly, 2.0% ectoine reversed their alternations and restored IL-13/IFN-γ balance.
CONCLUSIONS
Our findings demonstrate that topical ectoine significantly reduces corneal damage, and enhances goblet cell density and mucin production through restoring imbalanced IL-13/IFN-γ signaling in murine dry eye model. This suggests therapeutic potential of natural osmoprotectant ectoine for dry eye disease.
Topics: Animals; Dry Eye Syndromes; Mice; Mice, Inbred C57BL; Disease Models, Animal; Goblet Cells; Interferon-gamma; Mucins; Interleukin-13; Conjunctiva; Enzyme-Linked Immunosorbent Assay; Female; Epithelium, Corneal; Real-Time Polymerase Chain Reaction; RNA, Messenger; Amino Acids, Diamino
PubMed: 38935032
DOI: 10.1167/iovs.65.6.39 -
Oncology Research and Treatment Jun 2024Anal mucinous adenocarcinoma (AMAC) is an extremely rare form of anal cancer. Our objective was to examine the incidence, management, and prognostic factors of AMAC.
BACKGROUND
Anal mucinous adenocarcinoma (AMAC) is an extremely rare form of anal cancer. Our objective was to examine the incidence, management, and prognostic factors of AMAC.
MATERIALS AND METHODS
We analyzed age-adjusted incidence rates (AAI) over time and compared the prognosis of AMAC with anal squamous cell carcinoma (ASCC) and adenocarcinoma (AAC) using propensity score matching (PSM) and Kaplan-Meier analysis. Patients were classified based on summary stage and treatments to determine cancer-specific survival (CSS).
RESULTS
AAI of AMAC fluctuated within a narrow range (0.082-0.237 per million person-years) from 2000 to 2018. AMAC had a slight non-significant trend of worse prognosis than ASCC (p=0.348) and a better prognosis than AAC (p<0.01). Females made up a larger proportion of patients diagnosed with the distant disease (p<0.05) and unmarried (p<0.05), and somewhat less probably to need surgical removal (p<0.01) and radiotherapy (p<0.01). Elderly patients, with regional stage, distant-stage disease, no surgery tended to have lower rates of survival (all p<0.05). Localized stage was associated with better prognosis (p<0.05). Surgery was associated with a tendency towards better survival (p=0.095).
CONCLUSIONS
The incidence of AMAC is consistently low. AMAC demonstrates a more favorable prognosis compared to typical AAC and a slightly worse prognosis compared to ASCC. Females with AMAC were less likely to undergo surgical removal or receive radiotherapy. AMAC exhibits a low incidence yet favorable prognosis compared to typical AAC and slightly worse compared to ASCC. Elderly age is associated with poorer prognosis, while localized stage indicates better prognosis. Surgery demonstrates a trend towards improved survival.
PubMed: 38934176
DOI: 10.1159/000539930 -
Cureus May 2024The concurrent presentation of a low-grade appendiceal mucinous neoplasm (LAMN) and a borderline Brenner tumor (BT) of the ovary are exceedingly rare. Brenner tumors...
The concurrent presentation of a low-grade appendiceal mucinous neoplasm (LAMN) and a borderline Brenner tumor (BT) of the ovary are exceedingly rare. Brenner tumors stand out as a particularly uncommon form, making up only around 5% of all benign epithelial tumors of the ovary. Among the ovarian Brenner, the borderline subtype is even rarer. Appendiceal neoplasm (LAMN) and right ovarian BT cannot be distinguished due to their anatomical position. LAMN is often an incidental finding and at later stages when left undiagnosed may lead to pseudomyxoma peritonei (PMP). This case describes a postmenopausal woman in her 50s experiencing abdominal pain and bloating for a week. Elevated carcinoembryonic antigen (CEA) levels and imaging suggested a potential right ovarian tumor. Interestingly, it revealed a unique combination of borderline Brenner tumor of the right ovary and low-grade appendiceal mucinous neoplasm.
PubMed: 38933633
DOI: 10.7759/cureus.61151 -
Frontiers in Oncology 2024MUC21, also known as Epiglycanin, is a high-molecular-weight glycoprotein with transmembrane mucin properties. It consists of a tandem repeat domain, a stem domain, a... (Review)
Review
MUC21, also known as Epiglycanin, is a high-molecular-weight glycoprotein with transmembrane mucin properties. It consists of a tandem repeat domain, a stem domain, a transmembrane domain and a cytoplasmic tail. MUC21 is expressed is observed in normal tissues in organs like the thymus, testes, lungs, and large intestine. Research has shown that MUC21 is expressed in esophageal squamous cell carcinoma, lung adenocarcinoma, glioblastoma, thyroid cancer, melanoma, and various other malignant tumors in distinctive manner. Additionally, tumor invasion, metastasis, and poor prognosis are linked to it. Some researchers believe that MUC21 has the potential to become a new target in cancer treatment. This review aims to deliver a comprehensive overview of the glycosylation, function, and research progress of MUC21 in multiple types of cancer and infectious diseases.
PubMed: 38933439
DOI: 10.3389/fonc.2024.1410761 -
Frontiers in Immunology 2024Allergic sensitization is an essential step in the development of allergic airway inflammation to birch pollen (BP); however, this process remains to be fully...
INTRODUCTION & OBJECTIVE
Allergic sensitization is an essential step in the development of allergic airway inflammation to birch pollen (BP); however, this process remains to be fully elucidated. Recent scientific advances have highlighted the importance of the allergen context. In this regard, microbial patterns (PAMPs) present on BP have attracted increasing interest. As these PAMPs are recognized by specialized pattern recognition receptors (PRRs), this study aims at investigating the roles of intracellular PRRs and the inflammasome regulator NLRP3.
METHODS
We established a physiologically relevant intranasal and adjuvant-free sensitization procedure to study BP-induced systemic and local lung inflammation.
RESULTS
Strikingly, BP-sensitized -deficient mice showed significantly lower IgE levels, Th2-associated cytokines, cell infiltration into the lung, mucin production and epithelial thickening than their wild-type counterparts, which appears to be independent of inflammasome formation. Intriguingly, bone-marrow chimera revealed that expression of NLRP3 in the hematopoietic system is required to trigger an allergic response.
CONCLUSION
Overall, this study identifies NLRP3 as an important driver of BP-induced allergic immune responses.
Topics: Animals; NLR Family, Pyrin Domain-Containing 3 Protein; Pollen; Betula; Mice; Mice, Knockout; Administration, Intranasal; Allergens; Disease Models, Animal; Inflammasomes; Mice, Inbred C57BL; Cytokines; Hypersensitivity; Plant Extracts; Immunoglobulin E
PubMed: 38933263
DOI: 10.3389/fimmu.2024.1393819 -
Journal of Agricultural and Food... Jun 2024The human intestinal mucus layer protects against pathogenic microorganisms and harmful substances, whereas it also provides an important colonization niche for...
The human intestinal mucus layer protects against pathogenic microorganisms and harmful substances, whereas it also provides an important colonization niche for mutualistic microbes. The main functional components of mucus are heavily glycosylated proteins, called mucins. Mucins can be cleaved and utilized by intestinal microbes. The mechanisms between intestinal microbes and the regulation of mucin glycosylation are still poorly understood. In this study, mucus was produced by HT29-MTX-E12 cells under Semi-Wet interface with Mechanical Stimulation. Cells were exposed to pasteurized nonpathogenic bacteria , , and to evaluate influence on glycosylation patterns. Following an optimized protocol, O- and N-glycans were efficiently and reproducibly released, identified, and semiquantified using MALDI-TOF-MS and PGC-LC-MS/MS. Exposure of cells to bacteria demonstrated increased diversity of sialylated O-glycans and increased abundance of high mannose N-glycans in produced mucus. Furthermore, changes in glycan ratios were observed. It is speculated that bacterial components interact with the enzymatic processes in glycan production and that pasteurized bacteria influence glycosyltransferases or genes involved. These results highlight the influence of pasteurized bacteria on glycosylation patterns, stress the intrinsic relationship between glycosylation and microbiota, and show the potential of using produced mucus to study glycosylation behavior.
PubMed: 38932522
DOI: 10.1021/acs.jafc.4c01401 -
Polymers Jun 2024MUC2 mucin, the primary gel-forming component of intestinal mucus, is well researched and a model of polymerisation and post-secretory organisation has been published... (Review)
Review
MUC2 mucin, the primary gel-forming component of intestinal mucus, is well researched and a model of polymerisation and post-secretory organisation has been published previously. Recently, several significant developments have been made which either introduce new ideas or challenge previous theories. New ideas include an overhaul of the MUC2 C-terminal globular structure which is proposed to harbour several previously unobserved domains, and include a site for an extra intermolecular disulphide bridge dimer between the cysteine 4379 of adjacent MUC2 C-termini. MUC2 polymers are also now thought to be secreted attached to the epithelial surface of goblet cells in the small intestine and removed following secretion via a metalloprotease meprin β-mediated cleavage of the von Willebrand D2 domain of the N-terminus. It remains unclear whether MUC2 forms intermolecular dimers, trimers, or both, at the N-termini during polymerisation, with several articles supporting either trimer or dimer formation. The presence of a firm inner mucus layer in the small intestine is similarly unclear. Considering this recent research, this review proposes an update to the previous model of MUC2 polymerisation and secretion, considers conflicting theories and data, and highlights the importance of this research to the understanding of MUC2 mucus layers in health and disease.
PubMed: 38932019
DOI: 10.3390/polym16121663 -
Molecules (Basel, Switzerland) Jun 2024The discovery and investigation of new natural compounds with antimicrobial activity are new potential strategies to reduce the spread of antimicrobial resistance. The...
The discovery and investigation of new natural compounds with antimicrobial activity are new potential strategies to reduce the spread of antimicrobial resistance. The presented study reveals, for the first time, the promising antibacterial potential of two fractions from mucus with an MW < 20 kDa and an MW > 20 kDa against five bacterial pathogens- 1085, 1897, 8691, 3915, and 8754. Using de novo sequencing, 16 novel peptides with potential antibacterial activity were identified in a fraction with an MW < 20 kDa. Some bioactive compounds in a mucus fraction with an MW > 20 kDa were determined via a proteomic analysis on 12% sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and bioinformatics. High homology with proteins and glycoproteins was found, with potential antibacterial activity in mucus proteins named aspernin, hemocyanins, H-lectins, and L-amino acid oxidase-like protein, as well as mucins (mucin-5AC, mucin-5B, mucin-2, and mucin-17). We hypothesize that the synergy between the bioactive components determined in the composition of the fraction > 20 kDa are responsible for the high antibacterial activity against the tested pathogens in concentrations between 32 and 128 µg/mL, which is comparable to vancomycin, but without cytotoxic effects on model eukaryotic cells of . Additionally, a positive effect, by reducing the levels of intracellular oxidative damage and increasing antioxidant capacity, on cells was found for both mucus extract fractions of . These findings may serve as a basis for further studies to develop a new antibacterial agent preventing the development of antibiotic resistance.
Topics: Anti-Bacterial Agents; Mucus; Microbial Sensitivity Tests; Peptides; Enterococcus faecalis; Enterococcus faecium; Bacillus cereus; Animals; Propionibacterium acnes; Salmonella enterica
PubMed: 38930951
DOI: 10.3390/molecules29122886 -
Journal of Clinical Medicine Jun 2024: Although the role of PET/CT imaging is well established in oncology, its diagnostic value in routine monitoring for recurrent colorectal cancer (CRC) is still...
: Although the role of PET/CT imaging is well established in oncology, its diagnostic value in routine monitoring for recurrent colorectal cancer (CRC) is still controversial. The aim was to evaluate the diagnostic value of F-18 FDG PET/CT in detecting recurrent CRC in correlation with CEA, CA 19-9 levels, and conventional imaging modalities (CIM). Between 2009 and 2023, a retrospective study was performed including 134 CRC patients referred for PET/CT imaging on the suspicion of recurrence, based on elevated CEA and/or CA 19-9 and/or equivocal CIM findings. According to our institution's Tumor Board CRC protocol, after the initial treatment, which was dependent on the TNM stage (neoadjuvant therapy, primary resection, or adjuvant treatment), patients underwent a standard 5-year surveillance including CEA and CA 19-9 measurements, CIM, and colonoscopy, every six months. The statistics, including univariate and multivariate analyses were conducted using the IBM SPSS 20.0 statistical software. -values < 0.05 were considered statistically significant. Recurrent CRC was confirmed in 54/134 (40.3%) patients with elevated tumor markers. PET/CT showed high diagnostic performance in detecting recurrent CRC with sensitivity, specificity, PPV, NPV, and accuracy of 94.4%, 82.5%, 78.5%, 95.7%, and 87.3%, respectively. The CEA showed a high sensitivity of 98.1% but both low specificity and accuracy of 15% and 48.5%, respectively. The sensitivity, specificity, and accuracy for CA 19-9 and CIM for diagnosis of CRC recurrence were 44.4%, 67.5%, 58.2%, and 51.9%, 98.8%, 79.9%, respectively. The AUC for PET/CT, elevated CEA levels, CIM, and elevated CA 19-9 levels was 0.885 (95% CI: 0.824-0.946; < 0.001), 0.844 (95% CI: 0.772-0.916; < 0.001), 0.753 (95% CI: 0.612-0.844; < 0.001), and 0.547 (95% CI: 0.442-0.652; = 0.358), respectively. Univariate analysis showed that both PET/CT and CIM positive results were highly associated with CRC recurrence ( < 0.001 and < 0.001, respectively). At the same time, gender, mucinous tumor type, presence of initial lymph node metastasis (N+), and presence of initial distant metastasis (M+) had no significance ( = 0.211, = 0.158, = 0.583, and = 0.201, respectively). Our multivariate analysis showed that independent predictors for CRC recurrence are positive PET/CT scans ( < 0.001), positive CIM results ( = 0.001), and elevated CA 19-9 levels ( = 0.023). Although CA 19-9 was not detected as a statistically significant predictor in the univariate analysis ( = 0.358), in a multivariate analysis it was recognized as a significant predicting factor in detecting the CRC recurrence ( = 0.023). F-18 FDG PET/CT showed high diagnostic efficacy in CRC recurrence detection, in correlation with CEA levels, CA 19-9 levels, and CIM. This imaging modality should be routinely integrated into the post-operative follow-op in patients with elevated tumor markers.
PubMed: 38930131
DOI: 10.3390/jcm13123602 -
Medicina (Kaunas, Lithuania) Jun 2024: This study aimed to elucidate the cytologic characteristics and diagnostic usefulness of endoscopic ultrasonography-fine needle aspiration cytology (EUS-FNAC) by... (Comparative Study)
Comparative Study
: This study aimed to elucidate the cytologic characteristics and diagnostic usefulness of endoscopic ultrasonography-fine needle aspiration cytology (EUS-FNAC) by comparing it with liquid-based preparation (LBP) and conventional smear (CS) in pancreas. : The diagnostic categories (I through VII) were classified according to the World Health Organization Reporting System for Pancreaticobiliary Cytopathology. Ten cytologic features, including nuclear and additional features, were evaluated in 53 cases subjected to EUS-FNAC. Nuclear features comprised irregular nuclear contours, nuclear enlargement, hypochromatic nuclei with parachromatin clearing, and nucleoli. Additional cellular features included isolated atypical cells, mucinous cytoplasm, drunken honeycomb architecture, mitosis, necrotic background, and cellularity. A decision tree analysis was conducted to assess diagnostic efficacy. : The diagnostic concordance rate between LBP and CS was 49.1% (26 out of 53 cases). No significant differences in nuclear features were observed between categories III (atypical), VI (suspicious for malignancy), and VII (malignant). The decision tree analysis of LBP indicated that cases with moderate or high cellularity and mitosis could be considered diagnostic for those exhibiting nuclear atypia. Furthermore, in CS, mitosis, isolated atypical cells, and necrotic background exerted a more significant impact on the diagnosis of EUS-FNAC. : Significant parameters for interpreting EUS-FNAC may differ between LBP and CS. While nuclear atypia did not influence the diagnosis of categories III, VI, and VII, other cytopathologic features, such as cellularity, mitosis, and necrotic background, may present challenges in diagnosing EUS-FNAC.
Topics: Humans; Endoscopic Ultrasound-Guided Fine Needle Aspiration; Male; Female; Middle Aged; Aged; Pancreas; Adult; Pancreatic Neoplasms; Cytodiagnosis; Aged, 80 and over; Cytology
PubMed: 38929547
DOI: 10.3390/medicina60060930