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Cellular and Molecular Gastroenterology... May 2024Type 2 innate lymphoid cells (ILC2s) and interleukin-13 (IL-13) promote the onset of spasmolytic polypeptide-expressing metaplasia (SPEM) cells. However, little is known...
BACKGROUND & AIMS
Type 2 innate lymphoid cells (ILC2s) and interleukin-13 (IL-13) promote the onset of spasmolytic polypeptide-expressing metaplasia (SPEM) cells. However, little is known about molecular effects of IL-13 in SPEM cells. We now sought to establish a reliable organoid model, Meta1 gastroids, to model SPEM cells in vitro. We evaluated cellular and molecular effects of ILC2s and IL-13 on maturation and proliferation of SPEM cells.
METHODS
We performed single-cell RNA sequencing to characterize Meta1 gastroids, which were derived from stomachs of Mist1-Kras transgenic mice that displayed pyloric metaplasia. Cell sorting was used to isolate activated ILC2s from stomachs of IL-13-tdTomato reporter mice treated with L635. Three-dimensional co-culture was used to determine the effects of ILC2s on Meta1 gastroids. Mouse normal or metaplastic (Meta1) and human metaplastic gastroids were cultured with IL-13 to evaluate cell responses. Air-Liquid Interface culture was performed to test long-term culture effects of IL-13. In silico analysis determined possible STAT6-binding sites in gene promoter regions. STAT6 inhibition was performed to corroborate STAT6 role in SPEM cells maturation.
RESULTS
Meta1 gastroids showed the characteristics of SPEM cell lineages in vitro even after several passages. We demonstrated that co-culture with ILC2s or IL-13 treatment can induce phosphorylation of STAT6 in Meta1 and normal gastroids and promote the maturation and proliferation of SPEM cell lineages. IL-13 upregulated expression of mucin-related proteins in human metaplastic gastroids. Inhibition of STAT6 blocked SPEM-related gene expression in Meta1 gastroids and maturation of SPEM in both normal and Meta1 gastroids.
CONCLUSIONS
IL-13 promotes the maturation and proliferation of SPEM cells consistent with gastric mucosal regeneration.
PubMed: 38815928
DOI: 10.1016/j.jcmgh.2024.101366 -
World Journal of Gastrointestinal... May 2024We recently read with great interest a study by Zhang in the W. In our practice, we focus specifically on examining appendiceal mucinous neoplasms (AMNs) with...
We recently read with great interest a study by Zhang in the W. In our practice, we focus specifically on examining appendiceal mucinous neoplasms (AMNs) with endoscopic ultrasound (EUS) using different scopes. AMNs are rare neoplastic lesions characterized by an accumulation of mucin inside a cystic dilatation of the appendix. Clinically, they can present as nonspecific acute appendicitis. AMNs can turn into a life-threatening condition, termed pseudomyxoma peritonei, in which the ruptured appendix causes accumulation of mucin in the abdomen. Therefore, accurate and rapid diagnosis of AMN is essential. EUS is able to confirm and stage AMNs; although, EUS examination was once limited to the rectal and anal regions due to the conventional oblique-view scopes. With the emergence of new forward-view linear echoendoscopes and instruments like EUS miniprobes and overtubes, the scope of examination is changing. Herein, we discuss the feasibility of using the curved linear array echoendoscopes to examine cecal and appendiceal orifice lesions.
PubMed: 38813577
DOI: 10.4253/wjge.v16.i5.232 -
BMC Cancer May 2024The aim is to establish and verify reference intervals (RIs) for serum tumor markers for an apparently healthy elderly population in Southwestern China using an indirect...
BACKGROUND
The aim is to establish and verify reference intervals (RIs) for serum tumor markers for an apparently healthy elderly population in Southwestern China using an indirect method.
METHODS
Data from 35,635 apparently healthy elderly individuals aged 60 years and above were obtained in West China Hospital from April 2020 to December 2021. We utilized the Box-Cox conversion combined with the Tukey method to normalize the data and eliminate outliers. Subgroups are divided according to gender and age to examine the division of RIs. The Z-test was used to compare differences between groups, and 95% distribution RIs were calculated using a nonparametric method.
RESULTS
In the study, we observed that the RIs for serum ferritin and Des-γ-carboxy prothrombin (DCP) were wider for men, ranging from 64.18 to 865.80 ng/ml and 14.00 to 33.00 mAU/ml, respectively, compared to women, whose ranges were 52.58 to 585.88 ng/ml and 13.00 to 29.00 mAU/ml. For other biomarkers, the overall RIs were established as follows: alpha-fetoprotein (AFP) 0-6.75 ng/ml, carcinoembryonic antigen (CEA) 0-4.85 ng/ml, carbohydrate antigen15-3 (CA15-3) for females 0-22.00 U/ml, carbohydrate antigen19-9 (CA19-9) 0-28.10 U/ml, carbohydrate antigen125 (CA125) 0-20.96 U/ml, cytokeratin 19 fragment (CYFRA21-1) 0-4.66 U/ml, neuron-specific enolase (NSE) 0-19.41 ng/ml, total and free prostate-specific antigens (tPSA and fPSA) for males 0-5.26 ng/ml and 0-1.09 ng/ml. The RIs for all these biomarkers have been validated through our rigorous processes.
CONCLUSION
This study preliminarily established 95% RIs for an apparently healthy elderly population in Southwestern China. Using real-world data and an indirect method, simple and reliable RIs for an elderly population can be both established and verified, which are suitable for application in various clinical laboratories.
Topics: Humans; Male; Female; Aged; Biomarkers, Tumor; China; Reference Values; Middle Aged; Aged, 80 and over; Prothrombin; Neoplasms; alpha-Fetoproteins; Ferritins; CA-19-9 Antigen; Carcinoembryonic Antigen; CA-125 Antigen; Phosphopyruvate Hydratase; Keratin-19; Protein Precursors; Biomarkers
PubMed: 38811867
DOI: 10.1186/s12885-024-12408-1 -
BMC Oral Health May 2024This longitudinal study assessed the association between salivary protein composition and the clinical onset/severity of oral mucositis (OM) in patients with head and...
INTRODUCTION
This longitudinal study assessed the association between salivary protein composition and the clinical onset/severity of oral mucositis (OM) in patients with head and neck tumours treated with intensity-modulated-radiotherapy (IMRT).
METHODS
Saliva samples/clinical data were obtained from 40 head and neck cancer patients treated at Guy's Hospital before -IMRT(T0) and after-IMRT (T1 = 6 m, T2 = 12 m) (ethics approval/consent). Salivary flow rate, total protein concentration, and secretion rate were determined from saliva samples and compared with pre-treatment values. OM was assessed, total/specific salivary proteins, including mucin 5B and 7, IgA, cystatin-S, albumin, and α-amylase, were quantified.
RESULTS
95% patients experienced OM during IMRT, with 33 subjects reaching grade 2&3. At T1, there was a significant reduction in salivary flow rate, total protein secretion rate, α-amylase and cystatin-S compared to baseline. Remarkably IMRT did not significantly alter mucin 5B and 7, or the IgA secretion rate at any time point. At T1, all the analyzed proteins were associated with the OM outcomes. In addition, there was a significant inverse correlation between IgA concentration at T0 and the severity of OM during IMRT.
CONCLUSION
This study revealed significant associations between several salivary proteins and OM in patients with head and neck cancer undergoing IMRT. Further longitudinal studies are needed to confirm these results.
CLINICAL SIGNIFICANCE
The study contributes to the understanding of certain salivary proteins association with OM. This could be the first step towards identifying potential salivary markers that could offer perspectives for personalized medicine approaches to improve their quality of life (QoL).
RESEARCH QUESTION
What is the association between salivary proteins and the occurrence and severity of OM in head and neck cancer patients?
AIM
To assess the association between salivary protein composition with the clinical onset/severity of oral mucositis (OM) in head and neck cancer patients treated with intensity modulated radiotherapy.
NULL HYPOTHESIS
There is no association between salivary proteins and onset/severity of OM in HNC patients.
Topics: Humans; Longitudinal Studies; Head and Neck Neoplasms; Stomatitis; Male; Salivary Proteins and Peptides; Female; Middle Aged; Radiotherapy, Intensity-Modulated; Aged; Saliva; Adult; alpha-Amylases
PubMed: 38811865
DOI: 10.1186/s12903-024-04400-9 -
Nature Communications May 2024The intestinal anaerobic bacterium Akkermansia muciniphila is specialized in the degradation of mucins, which are heavily O-glycosylated proteins that constitute the...
The intestinal anaerobic bacterium Akkermansia muciniphila is specialized in the degradation of mucins, which are heavily O-glycosylated proteins that constitute the major components of the mucus lining the intestine. Despite that adhesion to mucins is considered critical for the persistence of A. muciniphila in the human intestinal tract, our knowledge of how this intestinal symbiont recognizes and binds to mucins is still limited. Here, we first show that the mucin-binding properties of A. muciniphila are independent of environmental oxygen concentrations and not abolished by pasteurization. We then dissected the mucin-binding properties of pasteurized A. muciniphila by use of a recently developed cell-based mucin array that enables display of the tandem repeats of human mucins with distinct O-glycan patterns and structures. We found that A. muciniphila recognizes the unsialylated LacNAc (Galβ1-4GlcNAcβ1-R) disaccharide selectively on core2 and core3 O-glycans. This disaccharide epitope is abundantly found on human colonic mucins capped by sialic acids, and we demonstrated that endogenous A. muciniphila neuraminidase activity can uncover the epitope and promote binding. In summary, our study provides insights into the mucin-binding properties important for colonization of a key mucin-foraging bacterium.
Topics: Akkermansia; Humans; Mucins; Polysaccharides; Neuraminidase; Protein Binding; Glycosylation; Disaccharides; Verrucomicrobia; Epitopes; Bacterial Adhesion
PubMed: 38811534
DOI: 10.1038/s41467-024-48770-8 -
Journal of Biomedical Research May 2024The intestinal mucosal barrier serves as a vital guardian for gut health, maintaining a delicate equilibrium between gut microbiota and host immune homeostasis. Recent...
The intestinal mucosal barrier serves as a vital guardian for gut health, maintaining a delicate equilibrium between gut microbiota and host immune homeostasis. Recent studies have found the intricate roles of Gasdermin D (GSDMD), a key executioner of pyroptosis downstream of the inflammasome, within the intestine, including controlling colitis in intestinal macrophage and the regulatory function in goblet cell mucus secretion. Thus, the exact role and nature of GSDMD's regulatory function in maintaining intestinal immune homeostasis and defending against pathogens remain elucidation. Here, we uncover that GSDMD plays a key role in defending against intestinal infection, with high expression in intestinal epithelial and lamina propria myeloid cells. Our results show that GSDMD specifically acts in intestinal epithelial cells to fight the infection, independently of its effects on antimicrobial peptides or mucin secretion. Instead, the resistance is mediated through GSDMD's N-terminal fragments, highlighting its importance in intestinal immunity. However, the specific underlying mechanism of GSDMD N-terminal activity in protection against intestinal bacterial infections still needs further study to clarify in the future.
PubMed: 38807373
DOI: 10.7555/JBR.38.20240041 -
Korean Journal of Radiology Jun 2024Incidental pancreatic cystic lesions are a common challenge encountered by diagnostic radiologists. Specifically, given the prevalence of benign pancreatic cystic... (Review)
Review
Incidental pancreatic cystic lesions are a common challenge encountered by diagnostic radiologists. Specifically, given the prevalence of benign pancreatic cystic lesions, determining when to recommend aggressive actions such as surgical resection or endoscopic ultrasound with sampling is difficult. In this article, we review the common types of cystic pancreatic lesions including serous cystadenoma, intraductal papillary mucinous neoplasm, and mucinous cystic neoplasm with imaging examples of each. We also discuss high-risk or worrisome imaging features that warrant a referral to a surgeon or endoscopist and provid several examples of these features. These imaging features adhere to the latest guidelines from the International Consensus Guidelines, American Gastroenterological Association (2015), American College of Gastroenterology (2018), American College of Radiology (2010, 2017), and European Guidelines (2013, 2018). Our focused article addresses the imaging dilemma of managing incidental cystic pancreatic lesions, weighing the options between imaging follow-up and aggressive interventions.
Topics: Humans; Pancreatic Cyst; Incidental Findings; Pancreatic Neoplasms; Diagnosis, Differential; Pancreas; Tomography, X-Ray Computed
PubMed: 38807337
DOI: 10.3348/kjr.2024.0085 -
Heliyon May 2024The main component of O-glycoproteins, mucin, is known to play important roles in physiological conditions and oncogenic processes, particularly correlated with poor...
The main component of O-glycoproteins, mucin, is known to play important roles in physiological conditions and oncogenic processes, particularly correlated with poor prognosis in different carcinomas. Diffuse-type gastric cancer (DGC) has long been associated with genomic stability and unfavorable clinical outcomes. To investigate further, we obtained clinical information and the RNA-seq data of the TCGA-STAD cohort. Through the use of unsupervised clustering methods and GSEA, we identified two distinct clusters, characterized by higher and lower expression of MUC2 and MUC20, denoted as cluster 1 and cluster 2, respectively. Subsequently, employing CIBERSORT, it was determined that cluster 2 exhibited a higher tumor mutation burden (TMB) and a greater abundance of CD8 T cells and activated CD4 memory T cells, in addition to immune checkpoints (ICPs). On the other hand, cluster 1 showed a lower TIDE score estimation, indicating a higher probability of tumor immune escape. Furthermore, overexpression of MUC15 and MUC20 was confirmed through qPCR and Western blotting, and their specific roles in mediating the epithelial-mesenchymal transition (EMT) process of GC cells (SNU484 and Hs746t) were validated via CCK-8 assay and wound healing assay in vitro. These findings highlight the potential prognostic value of MUC20 and offer insights into the prospects of immunotherapy for DGC by targeting MUC20.
PubMed: 38803848
DOI: 10.1016/j.heliyon.2024.e31403 -
Cureus Apr 2024A metastatic condition involving signet ring cells rich in mucin is the Krukenberg tumor, which affects the ovaries. Usually, the metastatic disease does not include...
A metastatic condition involving signet ring cells rich in mucin is the Krukenberg tumor, which affects the ovaries. Usually, the metastatic disease does not include both ovaries and usually originates from the stomach side, while it can also occur less frequently from other locations. Krukenberg tumors are uncommon in younger age groups and usually occur after the age of 40. We report a case of a 34-year-old female patient with a primary form of past medical history. The patient was treated with multiple rounds of chemotherapy.
PubMed: 38800331
DOI: 10.7759/cureus.59001 -
Plastic and Reconstructive Surgery.... May 2024Breast cancer is a leading cause of cancer among cisgender women worldwide, with an incidence that continues to rise. Breast reconstruction is increasingly recognized as...
Breast cancer is a leading cause of cancer among cisgender women worldwide, with an incidence that continues to rise. Breast reconstruction is increasingly recognized as an integral part of breast cancer management. In tandem, the population of trans women is also increasing. However, few studies have focused on the management of breast cancer in this population, given that estrogen therapy has the potential to increase the risk of breast cancer. We present the case of a 51-year-old trans woman diagnosed with right breast cancer following a 32-year history of estrogen therapy. She presented to our clinic for consultation and immediate breast reconstruction. She opted for bilateral skin-sparing mastectomies, sentinel lymph node biopsies, and immediate breast reconstruction using deep inferior epigastric perforator free flaps. There were no postoperative flap complications. Final pathology revealed invasive mucinous carcinoma, devoid of lymph node involvement. The patient was satisfied with her reconstruction and is currently planning for nipple reconstruction. To the authors' knowledge, this is the first reported case in the literature of bilateral deep inferior epigastric perforator free flap reconstruction in the trans female population after breast cancer diagnosis. This case underscores the need for a holistic treatment approach and heightened vigilance among trans women on estrogen therapy. It also highlights that breast reconstruction should be considered and offered to this patient population.
PubMed: 38798942
DOI: 10.1097/GOX.0000000000005834