• non-small-cell lung cancer
• tumour biomarkers

• 2023 Basic scientific research expenses scientific research projects of universities of Heilongjiang province (NO. 2023-KYYWF-0182).

• biomarkers
• diffusion‐weighted magnetic resonance imaging
• epithelial ovarian cancer
• sensitivity and specificity

• Humans
• Female
• Ovarian Neoplasms/blood
• Ovarian Neoplasms/diagnosis
• Ovarian Neoplasms/pathology
• Ovarian Neoplasms/diagnostic imaging
• Diffusion Magnetic Resonance Imaging/methods
• Mucin-1/blood
• Middle Aged
• Carcinoma, Ovarian Epithelial/blood
• Adult
• Biomarkers, Tumor/blood
• Neoplasms, Glandular and Epithelial/blood
• Neoplasms, Glandular and Epithelial/diagnosis
• Neoplasms, Glandular and Epithelial/pathology
• Neoplasms, Glandular and Epithelial/diagnostic imaging
• Aged
• Diagnosis, Differential
• Mucins/blood
• Membrane Proteins/blood
• CA-125 Antigen

• biomarkers
• molecular targeted treatment
• predictive markers
• prognostic marker

• CA-125
• endometrial cancer
• meta – analysis
• prognosis
• survival

• antibiotics
• antibiotics effect on gastrointestinal (GI) tract
• cyanine 3
• ex vivo mucus viscosity
• fluorescent molecular rotors
• mucus nanoviscosity

• Animals
• Anti-Bacterial Agents/pharmacology
• Mucus/chemistry
• Mucus/metabolism
• Viscosity
• Mice
• Carbocyanines/chemistry
• Swine
• Intestinal Mucosa/metabolism
• Intestinal Mucosa/drug effects
• Intestinal Mucosa/microbiology
• Mucins/metabolism
• Mucins/chemistry

• SFB 1449 Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)
• 431232613 Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)

• HER2
• anti-HER2 therapy resistance
• anti-HER2-therapy
• biomarker
• breast cancer
• combination therapy

• Cancer
• Galectin
• Immune cell
• Protein interaction

• Humans
• Galectins/metabolism
• Animals
• Neoplasms/metabolism
• Neoplasms/etiology
• Neoplasms/pathology
• Protein Binding
• Disease Susceptibility
• Inflammation/metabolism
• Intracellular Space/metabolism

• Philipps-Universität Marburg (1009)

• Cancer
• Glycosylation
• MUC1
• Mucins
• TACAs

• Humans
• Mucin-1/metabolism
• Neoplasms/metabolism
• Neoplasms/immunology
• Neoplasms/pathology
• Animals
• Antigens, Tumor-Associated, Carbohydrate/metabolism
• Antigens, Tumor-Associated, Carbohydrate/immunology
• Glycosylation
• Epitopes/immunology

• ascites burden
• carbohydrate antigen 125 kinetics
• gastric cancer
• peritoneal metastases

• Antibody drug conjugate
• Bispecific T-cell engager
• CA125
• Chimeric antigen receptor-T cells
• Crystal structure
• MUC16
• Ovarian cancer

• Female
• Humans
• CA-125 Antigen/metabolism
• Membrane Proteins/metabolism
• Ovarian Neoplasms/pathology
• Antigen-Antibody Reactions

• P30 CA008748 NCI NIH HHS
• P30 GM124165 NIGMS NIH HHS
• The Julie Fund
• National Institutes of Health grant
• NIH-ORIP HEI
• Congressionally Directed Medical Research Programs
• Nile Albright Research Foundation
• The Flatley Foundation
• The Worden Family Foundation

• MUC1
• MUC16
• immunotherapy
• mucins
• targeted drug therapy
• tumor microenvironment

• Animals
• Mucin-1/metabolism
• CA-125 Antigen/metabolism
• Mucins
• Neoplasms/drug therapy
• Immunity
• Mammals/metabolism
• Tumor Microenvironment

• MUC1
• cancer
• combination therapy
• immunotherapy
• targeted therapy

• Gastric cancer
• Genotype.
• H. pylori
• MUC1 5640G>A polymorphism
• PCR-RFLP

• MUC
• cell membrane permeation
• intestinal absorption
• mucin
• mucus layer

• Gal-3
• MUC1
• TACAs
• cancer
• galectins
• glycosylation
• mucins

• SUB-1-DN-22-001-2203 Medical University of Białystok

• Biomarkers
• Fluorescence
• Intraoperative molecular imaging
• Mucins
• Optical surgical navigation

• Humans
• Contrast Media
• Fluorescence
• Mucins
• Pancreatic Neoplasms/diagnostic imaging
• Pancreatic Neoplasms/surgery
• Surgery, Computer-Assisted/methods
• Proteins
• Optical Imaging/methods

• P20 GM121316 NIGMS NIH HHS
• R01 CA208108 NCI NIH HHS
• R01 CA256973 NCI NIH HHS
• P30 CA036727 NCI NIH HHS
• P01 CA217798 NCI NIH HHS
• R01 CA259080 NCI NIH HHS
• U01 CA210240 NCI NIH HHS

• Lewis’s antigen
• N-glycosylation
• O-glycosylation
• T antigen
• Tn antigen
• bladder cancer
• extracellular vesicles
• glycosaminoglycans
• mucins
• tumor glycosylation

• N18/DBS/000007 Jagiellonian University

• Ciliopathies
• OFD1
• cilia
• gene expression
• protein degradation
• protein synthesis

• adenocarcinoma
• adenoma
• adenomatous polyps
• colorectal cancer
• hyperplastic polyps
• mucinous carcinoma
• mucins
• prognostics
• serrated polyps

• I01 BX003856 BLRD VA
• T32 CA121938 NCI NIH HHS
• T32CA121938 NIH HHS
• R01 CA256973 NCI NIH HHS
• I01 BX004494 BLRD VA

• barrier function
• biological characteristics
• health and illness
• mucin
• mucus
• phenotypic switch

Peritoneal metastasis (PM) after primary surgery for colorectal cancer (CRC) has the worst prognosis. Prediction and early detection of metachronous PM (m-PM) have an important role in improving postoperative prognosis of CRC. However, commonly used imaging methods have limited sensitivity to detect PM early. We aimed to establish a nomogram model to evaluate the individual probability of m-PM to facilitate early interventions for high-risk patients.

To establish and validate a nomogram model for predicting the occurrence of m-PM in CRC within 3 years after surgery.

We used the clinical data of 878 patients at the Second Hospital of Jilin University, between January 1, 2014 and January 31, 2019. The patients were randomly divided into training and validation cohorts at a ratio of 2:1. The least absolute shrinkage and selection operator (LASSO) regression was performed to identify the variables with nonzero coefficients to predict the risk of m-PM. Multivariate logistic regression was used to verify the selected variables and to develop the predictive nomogram model. Harrell’s concordance index, receiver operating characteristic curve, Brier score, and decision curve analysis (DCA) were used to evaluate discrimination, distinctiveness, validity, and clinical utility of this nomogram model. The model was verified internally using bootstrapping method and verified externally using validation cohort.

LASSO regression analysis identified six potential risk factors with nonzero coefficients. Multivariate logistic regression confirmed the risk factors to be independent. Based on the results of two regression analyses, a nomogram model was established. The nomogram included six predictors: Tumor site, histological type, pathological T stage, carbohydrate antigen 125, v-raf murine sarcoma viral oncogene homolog B mutation and microsatellite instability status. The model achieved good predictive accuracy on both the training and validation datasets. The C-index, area under the curve, and Brier scores were 0.796, 0.796 [95% confidence interval (CI) 0.735-0.856], and 0.081 for the training cohort and 0.782, 0.782 (95%CI 0.690-0.874), and 0.089 for the validation cohort, respectively. DCA showed that when the threshold probability was between 0.01 and 0.90, using this model to predict m-PM achieved a net clinical benefit.

We have established and validated a nomogram model to predict m-PM in patients undergoing curative surgery, which shows good discrimination and high accuracy.

• Colorectal cancer
• Metachronous peritoneal metastasis
• Risk factor
• Nomogram

• glycosyltransferases
• goblet cells
• gut barrier
• gut microbiota
• high-fat diet
• mucins
• mucus
• obesity
• oligosaccharides
• type 2 diabetes

• PI3K/AKT/NF-κB signaling pathway
• lipopolysaccharide
• mucous layer
• tight junction protein
• uterus

• Animals
• Cadherins
• Endometrium/metabolism
• Endotoxins
• Female
• Glycosaminoglycans
• Lipopolysaccharides/toxicity
• Mice
• Mucins
• NF-kappa B/metabolism
• Phosphatidylinositol 3-Kinases/metabolism
• Pregnancy
• Proto-Oncogene Proteins c-akt/metabolism

• 2020-NY-020 Shaanxi University of Technology

Mucinases of human gut bacteria cleave peptide bonds in mucins strictly depending on the presence of neighboring O-glycans. The Akkermansia muciniphila AM0627 mucinase cleaves specifically in between contiguous (bis) O-glycans of defined truncated structures, suggesting that this enzyme may recognize clustered O-glycan patches. Here, we report the structure and molecular mechanism of AM0627 in complex with a glycopeptide containing a bis-T (Galβ1-3GalNAcα1-O-Ser/Thr) O-glycan, revealing that AM0627 recognizes both the sugar moieties and the peptide sequence. AM0627 exhibits preference for bis-T over bis-Tn (GalNAcα1-O-Ser/Thr) O-glycopeptide substrates, with the first GalNAc residue being essential for cleavage. AM0627 follows a mechanism relying on a nucleophilic water molecule and a catalytic base Glu residue. Structural comparison among mucinases identifies a conserved Tyr engaged in sugar-π interactions in both AM0627 and the Bacteroides thetaiotaomicron BT4244 mucinase as responsible for the common activity of these two mucinases with bis-T/Tn substrates. Our work illustrates how mucinases through tremendous flexibility adapt to the diversity in distribution and patterns of O-glycans on mucins.

AM0627 is a bis-O-glycan mucinase that might work in the final steps of mucus degradation, thereby providing a carbon and nitrogen source for Akkermansia muciniphila. Here, the authors provide molecular insights into AM0627 function from X-ray crystallography and computer simulations.

• MUC4
• polymorphisms
• recurrent pregnancy loss

• Abortion, Habitual/genetics
• Case-Control Studies
• Female
• Humans
• Mucin-4/genetics
• Polymorphism, Single Nucleotide/genetics
• Pregnancy
• Republic of Korea

• cancer
• cell migration
• metastasis

• Autophagy
• Epithelial-Mesenchymal Transition (EMT)
• Metastasis
• Starvation
• Tumor signalling pathways

• ALSPAC
• Asthma acquisition
• DNA methylation
• Epigenome-wide
• IOWBC

• Adolescent
• Adult
• Asthma/diagnosis
• Asthma/genetics
• Child
• CpG Islands
• DNA Methylation
• Epigenesis, Genetic
• Epigenomics
• Female
• Genome-Wide Association Study
• Humans
• Infant, Newborn
• Ligases/genetics
• Longitudinal Studies
• Male
• Polycomb-Group Proteins/genetics
• Receptors, Interleukin/genetics
• Young Adult

• 217065/Z/19/Z Wellcome Trust
• MC_UU_00011/5 Medical Research Council
• MC_PC_19009 Medical Research Council
• MC_PC_15018 Medical Research Council
• R01 AI121226 NIAID NIH HHS
• G9815508 Medical Research Council
• Wellcome Trust
• R01 HL132321 NHLBI NIH HHS
• R01 AI091905 NIAID NIH HHS

• Drug resistance
• Intracellular mucin 20
• Mitochondrial calcium homeostasis
• Mitochondrial membrane potential
• Signet ring cell carcinoma

• Animals
• Calcium/therapeutic use
• Carcinoma, Signet Ring Cell/pathology
• Cisplatin
• Drug Resistance
• Heterografts
• Homeostasis
• Humans
• Mice
• Mucins
• Stomach Neoplasms/drug therapy
• Stomach Neoplasms/genetics
• Stomach Neoplasms/metabolism

• Evolution
• Extracellular
• Galectin
• Glycan binding protein
• Glycobiology
• Immunology
• Intracellular
• Microbes

• Mucin 20
• TME
• ccRCC
• prognostic biomarker
• tumor-infiltrating immune cell

We analyzed, for the first time, the major components and biological properties of the venom of Vespa bicolor, a wasp from South China. Using HPLC and SDS-PAGE, combined with LC–MS/MS, MALDI-TOF-MS, and NMR data to analyze V. bicolor venom (VBV), we found that VBV contains three proteins (hyaluronidase A, phospholipase A1 (two isoforms), and antigen 5 protein) with allergenic activity, two unreported proteins (proteins 5 and 6), and two active substances with large quantities (mastoparan-like peptide 12a (Vb-MLP 12a), and 5-hydroxytryptamine (5-HT)). In addition, the antimicrobial activity of VBV was determined, and results showed that it had a significant effect against anaerobic bacteria. The minimum inhibitory concentration and minimum bactericidal concentration for Propionibacterium acnes were 12.5 µg/mL. Unsurprisingly, VBV had strong antioxidant activity because of the abundance of 5-HT. Contrary to other Vespa venom, VBV showed significant anti-inflammatory activity, even at low concentrations (1 µg/mL), and we found that Vb-MLP 12a showed pro-inflammatory activity by promoting the proliferation of RAW 264.7 cells. Cytotoxicity studies showed that VBV had similar antiproliferative effects against all tested tumor cell lines (HepG2, Hela, MCF-7, A549, and SASJ-1), with HepG2 being the most susceptible. Overall, this study on VBV has high clinical importance and promotes the development of Vespa bicolor resources.

• chromatography
• gel electrophoresis
• in vitro effect
• major component
• mass
• wasp venom

• A549 Cells
• Animals
• China
• HeLa Cells
• Hep G2 Cells
• Humans
• Insect Proteins/chemistry
• Insect Proteins/pharmacology
• MCF-7 Cells
• Microbial Sensitivity Tests
• Wasp Venoms/chemistry
• Wasp Venoms/pharmacology
• Wasps/chemistry

ORAL squamous cell carcinoma (OSCC) is a malignant tumor with the highest incidence among tumors involving the oral cavity maxillofacial region, and is notorious for its high recurrence and metastasis potential. Long non-coding RNAs (lncRNAs), which regulate the genesis and evolution of cancers, are potential prognostic biomarkers. This study identified HOTAIRM1 as a novel significantly upregulated lncRNA in OSCC, which is strongly associated with unfavorable prognosis of OSCC. Systematic bioinformatics analyses demonstrated that HOTAIRM1 was closely related to tumor stage, overall survival, genome instability, the tumor cell stemness, the tumor microenvironment, and immunocyte infiltration. Using biological function prediction methods, including Weighted gene co-expression network analysis (WGCNA), Gene set enrichment analysis (GSEA), and Gene set variation analysis (GSVA), HOTAIRM1 plays a pivotal role in OSCC cell proliferation, and is mainly involved in the regulation of the cell cycle. In vitro, cell loss-functional experiments confirmed that HOTAIRM1 knockdown significantly inhibited the proliferation of OSCC cells, and arrested the cell cycle in G1 phase. At the molecular level, PCNA and CyclinD1 were obviously reduced after HOTAIRM1 knockdown. The expression of p53 and p21 was upregulated while CDK4 and CDK6 expression was decreased by HOTAIRM1 knockdown. In vivo, knocking down HOTAIRM1 significantly inhibited tumor growth, including the tumor size, weight, volume, angiogenesis, and hardness, monitored by ultrasonic imaging and magnetic resonance imaging In summary, our study reports that HOTAIRM1 is closely associated with tumorigenesis of OSCC and promotes cell proliferation by regulating cell cycle. HOTAIRM1 could be a potential prognostic biomarker and a therapeutic target for OSCC.

• MUC 1
• aberrant glycosylation
• hepatocellular carcinoma
• highly glycosylated tumor-associated antigen (TAA)
• immune signaling
• immunotherapy

• Antigens, Neoplasm
• Biology
• Carcinoma, Hepatocellular/pathology
• Humans
• Immunotherapy/methods
• Liver Neoplasms/pathology
• Mucin-1

• CD8 T cells
• DNA vaccines
• MUC1
• Tumor retardation

• Animals
• CD8-Positive T-Lymphocytes
• DNA/genetics
• Humans
• Immunization
• Mice
• Mice, Inbred BALB C
• Mucin-1/genetics
• Mucin-1/immunology
• Mucin-1/therapeutic use
• Neoplasms/metabolism
• Plasmids/genetics
• Plasmids/therapeutic use
• Vaccination/methods

• Seoul National University Hospital

• Epithelium
• Goblet cell
• Mucin
• Ocular surface
• Tear film

• Animals
• Epithelial Cells/metabolism
• Eye/metabolism
• Humans
• Mucins/metabolism
• Ocular Physiological Phenomena
• Tears/metabolism
• Vision, Ocular/physiology

• R01 EY026147 NEI NIH HHS
• R01 EY030928 NEI NIH HHS

• Breast cancer
• Cancer immunotherapy
• DNA-based vaccine
• Dendritic cell vaccines
• Peptide-based vaccine

• Carcinoma, Non-Small-Cell Lung/drug therapy
• Chemoradiotherapy
• Humans
• Immunotherapy
• Lung Neoplasms/drug therapy
• Progression-Free Survival
• Randomized Controlled Trials as Topic

• MUC1
• apoptosis
• autophagy
• diisoquinoline derivative
• gastric cancer

• Antibody-drug conjugate
• DMUC4064A
• Ovarian cancer
• Platinum-resistant
• THIOMAB

• adaptive metabolism
• autophagy
• macropinocytosis
• mucins
• pancreatic carcinoma

The interorgan crosstalk between the liver and the intestine has been the focus of intense research. Key in this crosstalk are bile acids, which are secreted from the liver into the intestine, interact with the microbiome, and upon absorption reach back to the liver. The bile acid-activated farnesoid X receptor (Fxr) is involved in the gut-to-liver axis. However, liver-to-gut communication and the roles of bile acids and Fxr remain elusive. Herein, we aim to get a better understanding of Fxr-mediated liver-to-gut communication, particularly in colon functioning.

Fxr floxed/floxed mice were crossed with cre-expressing mice to yield Fxr ablation in the intestine (Fxr-intKO), liver (Fxr-livKO), or total body (Fxr-totKO). The effects on colonic gene expression (RNA sequencing), the microbiome (16S sequencing), and mucus barrier function by ex vivo imaging were analysed.

Despite relatively small changes in biliary bile acid concentration and composition, more genes were differentially expressed in the colons of Fxr-livKO mice than in those of Fxr-intKO and Fxr-totKO mice (3272, 731, and 1824, respectively). The colons of Fxr-livKO showed increased expression of antimicrobial genes, Toll-like receptors, inflammasome-related genes and genes belonging to the ‘Mucin-type O-glycan biosynthesis’ pathway. Fxr-livKO mice have a microbiome profile favourable for the protective capacity of the mucus barrier. The thickness of the inner sterile mucus layer was increased and colitis symptoms reduced in Fxr-livKO mice.

Targeting of FXR is at the forefront in the battle against metabolic diseases. We show that ablation of Fxr in the liver greatly impacts colonic gene expression and increased the colonic mucus barrier. Increasing the mucus barrier is of utmost importance to battle intestinal diseases such as inflammatory bowel disease, and we show that this might be done by antagonising FXR in the liver.

This study shows that the communication of the liver to the intestine is crucial for intestinal health. Bile acids are key players in this liver-to-gut communication, and when Fxr, the master regulator of bile acid homoeostasis, is ablated in the liver, colonic gene expression is largely affected, and the protective capacity of the mucus barrier is increased.

•

Fxr ablation in the mouse liver has a major impact on colonic gene expression.

• BAs, bile acids
• Colon
• DSS, dextran sodium sulfate
• FITC, fluorescein isothiocyanate
• Farnesoid X receptor
• Fgfr4, fibroblast growth factor receptor 4
• Fxr, farnesoid X receptor
• Fxr-intKO, intestine-specific Fxr knockout
• Fxr-livKO, liver-specific Fxr knockout
• Fxr-totKO, whole body Fxr knockout
• GO, Gene Ontology
• Gut microbiome
• HID, high-iron diamine
• IBD, inflammatory bowel disease
• Intestine-specific Fxr-KO mouse
• KEGG, Kyoto Encyclopedia of Genes and Genomes
• Liver-specific Fxr-KO mouse
• Liver–gut axis
• Mucus layer
• RT qPCR, real-time quantitative PCR
• fpkm, fragments per kilobase of transcript per million mapped reads

Mucoepidermoid carcinoma (MEC) is one of the most frequently misdiagnosed tumors. Glycans are modulated by malignant transformation. Mucin 1 (MUC1) is a mucin whose expression is upregulated in various tumors, including MEC, and it has previously been investigated as a diagnostic and prognostic tumor marker. The present study aimed to reveal the differences in the mucin glycans between MEC and normal salivary glands (NSGs) to discover novel diagnostic markers. Soluble fractions of salivary gland homogenate prepared from three MEC salivary glands and 7 NSGs were evaluated. Mucins in MEC and NSGs were separated using supported molecular matrix electrophoresis, and stained with Alcian blue and monoclonal antibodies. The glycans of the separated mucins were analyzed by mass spectrometry. MUC1 was found in MEC but not in NSGs, and almost all glycans of MUC1 in MEC were sialylated, whereas the glycans of mucins in NSGs were less sialylated. The core 2 type glycans, (Hex)₂(HexNAc)₂(NeuAc)₁ and (Hex)₂(HexNAc)₂(NeuAc)₂, were found to be significantly abundant glycans of MUC1 in MEC. MEC markedly produced MUC1 modified with sialylated core 2 glycans. These data were obtained from the soluble fractions of salivary gland homogenates. These findings provide a basis for the utilization of MUC1 as a serum diagnostic marker for the preoperative diagnosis of MEC.

• O-glycan
• mucin
• mucin 1
• mucoepidermoid carcinoma
• salivary gland