Sphingosine kinase 1-specific inhibitor PF543 reduces goblet cell metaplasia of bronchial epithelium in an acute asthma model.

Sphingosine kinase 1 (SPHK1) has been shown to play a key role in the pathogenesis of asthma where SPHK1-generated sphingosine-1-phosphate (S1P) is known to mediate innate and adaptive immunity while promoting mast cell degranulation. Goblet cell metaplasia (GCM) contributes to airway obstruction in asthma and has been demonstrated in animal models. We investigated the role of PF543, a SPHK1-specific inhibitor, in preventing the pathogenesis of GCM using a murine (C57BL/6) model of allergen-induced acute asthma. Treatment with PF543 before triple allergen exposure (DRA: House dust mite, Ragweed pollen, and Aspergillus) reduced inflammation, eosinophilic response, and GCM followed by reduced airway hyperreactivity to intravenous methacholine. Furthermore, DRA exposure was associated with increased expression of SPHK1 in the airway epithelium which was reduced by PF543. DRA-induced reduction of acetylated α-tubulin in airway epithelium was associated with an increased expression of NOTCH2 and SPDEF which was prevented by PF543. In vitro studies using human primary airway epithelial cells showed that inhibition of SPHK1 using PF543 prevented an allergen-induced increase of both NOTCH2 and SPDEF. siRNA silencing of SPHK1 prevented the allergen-induced increase of both NOTCH2 and SPDEF. NOTCH2 silencing was associated with a reduction of SPDEF but not that of SPHK1 upon allergen exposure. Our studies demonstrate that inhibition of SPHK1 protected allergen-challenged airways by preventing GCM and airway hyperreactivity, associated with downregulation of the NOTCH2-SPDEF signaling pathway. This suggests a potential novel link between SPHK1, GCM, and airway remodeling in asthma.NEW & NOTEWORTHY The role of SPHK1-specific inhibitor, PF543, in preventing goblet cell metaplasia (GCM) and airway hyperreactivity (AHR) is established in an allergen-induced mouse model. This protection was associated with the downregulation of NOTCH2-SPDEF signaling pathway, suggesting a novel link between SPHK1, GCM, and AHR.

Quercetin improves epithelial regeneration from airway basal cells of COPD patients.

BACKGROUND: Airway basal cells (BC) from patients with chronic obstructive pulmonary disease (COPD) regenerate abnormal airway epithelium and this was associated with reduced expression of several genes involved in epithelial repair. Quercetin reduces airway epithelial remodeling and inflammation in COPD models, therefore we examined whether quercetin promotes normal epithelial regeneration from COPD BC by altering gene expression. METHODS: COPD BC treated with DMSO or 1 µM quercetin for three days were cultured at air/liquid interface (ALI) for up to 4 weeks. BC from healthy donors cultured at ALI were used as controls. Polarization of cells was determined at 8 days of ALI. The cell types and IL-8 expression in differentiated cell cultures were quantified by flow cytometry and ELISA respectively. Microarray analysis was conducted on DMSO or 1 µM quercetin-treated COPD BC for 3 days to identify differentially regulated genes (DEG). Bronchial brushings obtained from COPD patients with similar age and disease status treated with either placebo (4 subjects) or 2000 mg/day quercetin (7 subjects) for 6 months were used to confirm the effects of quercetin on gene expression. RESULTS: Compared to placebo-, quercetin-treated COPD BC showed significantly increased transepithelial resistance, more ciliated cells, fewer goblet cells, and lower IL-8. Quercetin upregulated genes associated with tissue and epithelial development and differentiation in COPD BC. COPD patients treated with quercetin, but not placebo showed increased expression of two developmental genes HOXB2 and ELF3, which were also increased in quercetin-treated COPD BC with FDR < 0.001. Active smokers showed increased mRNA expression of TGF-ß (0.067) and IL-8 (22.0), which was reduced by 3.6 and 4.14 fold respectively after quercetin treatment. CONCLUSIONS: These results indicate that quercetin may improve airway epithelial regeneration by increasing the expression of genes involved in epithelial development/differentiation in COPD. TRIAL REGISTRATION: This study was registered at ClinicalTrials.gov on 6-18-2019. The study number is NCT03989271.

Seihaito, a Kampo medicine, attenuates IL-13-induced mucus production and goblet cell metaplasia.

Goblet cell hyperplasia and increased mucus production are features of airway diseases, including asthma, and excess airway mucus often worsens these conditions. Even steroids are not uniformly effective in mucus production in severe asthma, and new therapeutic options are needed. Seihaito is a Japanese traditional medicine that is used clinically as an antitussive and expectorant. In the present study, we examined the effect of Seihaito on goblet cell differentiation and mucus production. In in vitro studies, using air-liquid interface culture of guinea-pig tracheal epithelial cells, Seihaito inhibited IL-13-induced proliferation of goblet cells and MUC5AC, a major component of mucus production. Seihaito suppressed goblet cell-specific gene expression, without changing ciliary cell-specific genes, suggesting that it inhibits goblet cell differentiation. In addition, Seihaito suppressed MUC5AC expression in cells transfected with SPDEF, a transcription factor activated by IL-13. Furthermore, Seihaito attenuated in vivo goblet cell proliferation and MUC5AC mRNA expression in IL-13-treated mouse lungs. Collectively, these findings demonstrated that Seihaito has an inhibitory effect on goblet cell differentiation and mucus production, which is at least partly due to the inhibition of SPDEF.

Insights into the effects of chronic combined chromium-nickel exposure on colon damage in mice through transcriptomic analysis and in vitro gastrointestinal digestion assay.

Heavy metals interact with each other in a coexisting manner to produce complex combined toxicity to organisms. At present, the toxic effects of chronic co-exposure to heavy metals hexavalent chromium [Cr(VI)] and divalent nickel [Ni(II)] on organisms are seldom studied and the related mechanisms are poorly understood. In this study, we explored the mechanism of the colon injury in mice caused by chronic exposure to Cr or/and Ni. The results showed that, compared with the control group, Cr or/and Ni chronic exposure affected the body weight of mice, and led to infiltration of inflammatory cells in the colon, decreased the number of goblet cells, fusion of intracellular mucus particles and damaged cell structure of intestinal epithelial. In the Cr or/and Ni exposure group, the activity of nitric oxide synthase (iNOS) increased, the expression levels of MUC2 were significantly down-regulated, and those of ZO-1 and Occludin were significantly up-regulated. Interestingly, factorial analysis revealed an interaction between Cr and Ni, which was manifested as antagonistic effects on iNOS activity, ZO-1 and MUC2 mRNA expression levels. Transcriptome sequencing further revealed that the expression of genes-related to inflammation, intestinal mucus and tight junctions changed obviously. Moreover, the relative contents of Cr(VI) and Ni(II) in the Cr, Ni and Cr+Ni groups all changed with in-vitro gastrointestinal （IVG）digestion, especially in the Cr+Ni group. Our results indicated that the chronic exposure to Cr or/and Ni can lead to damage to the mice colon, and the relative content changes of Cr(VI) and Ni(II) might be the main reason for the antagonistic effect of Cr+Ni exposure on the colon damage.

Antenatal Ureaplasma Infection Causes Colonic Mucus Barrier Defects: Implications for Intestinal Pathologies.

Chorioamnionitis is a risk factor for necrotizing enterocolitis (NEC). Ureaplasma parvum (UP) is clinically the most isolated microorganism in chorioamnionitis, but its pathogenicity remains debated. Chorioamnionitis is associated with ileal barrier changes, but colonic barrier alterations, including those of the mucus barrier, remain under-investigated, despite their importance in NEC pathophysiology. Therefore, in this study, the hypothesis that antenatal UP exposure disturbs colonic mucus barrier integrity, thereby potentially contributing to NEC pathogenesis, was investigated. In an established ovine chorioamnionitis model, lambs were intra-amniotically exposed to UP or saline for 7 d from 122 to 129 d gestational age. Thereafter, colonic mucus layer thickness and functional integrity, underlying mechanisms, including endoplasmic reticulum (ER) stress and redox status, and cellular morphology by transmission electron microscopy were studied. The clinical significance of the experimental findings was verified by examining colon samples from NEC patients and controls. UP-exposed lambs have a thicker but dysfunctional colonic mucus layer in which bacteria-sized beads reach the intestinal epithelium, indicating undesired bacterial contact with the epithelium. This is paralleled by disturbed goblet cell MUC2 folding, pro-apoptotic ER stress and signs of mitochondrial dysfunction in the colonic epithelium. Importantly, the colonic epithelium from human NEC patients showed comparable mitochondrial aberrations, indicating that NEC-associated intestinal barrier injury already occurs during chorioamnionitis. This study underlines the pathogenic potential of UP during pregnancy; it demonstrates that antenatal UP infection leads to severe colonic mucus barrier deficits, providing a mechanistic link between antenatal infections and postnatal NEC development.

The Modulation of Respiratory Epithelial Cell Differentiation by the Thickness of an Electrospun Poly-ε-Carprolactone Mesh Mimicking the Basement Membrane.

The topology of the basement membrane (BM) affects cell physiology and pathology, and BM thickening is associated with various chronic lung diseases. In addition, the topology of commercially available poly (ethylene terephthalate) (PET) membranes, which are used in preclinical in vitro models, differs from that of the human BM, which has a fibrous and elastic structure. In this study, we verified the effect of BM thickness on the differentiation of normal human bronchial epithelial (NHBE) cells. To evaluate whether the thickness of poly-ε-carprolactone (PCL) mesh affects the differentiation of NHBE cells, cells were grown on thin- (6-layer) and thick-layer (80-layer) meshes consisting of electrospun PCL nanofibers using an air-liquid interface (ALI) cell culture system. It was found that the NHBE cells formed a normal pseudostratified epithelium composed of ciliated, goblet, and basal cells on the thin-layer PCL mesh; however, goblet cell hyperplasia was observed on the thick-layer PCL mesh. Differentiated NHBE cells cultured on the thick-layer PCL mesh also demonstrated increased epithelial-mesenchymal transition (EMT) compared to those cultured on the thin-layer PCL mesh. In addition, expression of Sox9, nuclear factor (NF)-κB, and oxidative stress-related markers, which are also associated with goblet cell hyperplasia, was increased in the differentiated NHBE cells cultured on the thick-layer PCL mesh. Thus, the use of thick electrospun PCL mesh led to NHBE cells differentiating into hyperplastic goblet cells via EMT and the oxidative stress-related signaling pathway. Therefore, the topology of the BM, for example, thickness, may affect the differentiation direction of human bronchial epithelial cells.

Aryl Hydrocarbon Receptor Regulates Muc2 Production Independently of IL-22 during Colitis.

We previously reported that an aryl hydrocarbon receptor (AhR) ligand, indole-3-carbinol (I3C), was effective at reducing colitis severity through immune cell-mediated interleukin-22 (IL-22) production. Intestinal epithelial cells (IECs) are also involved in regulating colitis, so we investigated their AhR-mediated mechanisms in the current report. A transcriptome analysis of IECs in wildtype (WT) mice revealed that during colitis, I3C regulated select mucin proteins, which could be attributed to goblet cell development. To address this, experiments under in vivo colitis (mice) or in vitro colon organoid conditions were undertaken to determine how select mucin proteins were altered in the absence or presence of AhR in IECs during I3C treatment. Comparing WT to IEC-specific AhR knockout mice (AhRΔIEC), the results showed that AhR expression was essential in IECs for I3C-mediated protection during colitis. AhR-deficiency also impaired mucin protein expression, particularly mucin 2 (Muc2), independently of IL-22. Collectively, this report highlights the important role of AhR in direct regulation of Muc2. These results provide justification for future studies aimed at determining how AhR might regulate select mucins through mechanisms such as direct transcription binding to enhance production.

A rare goblet cell adenocarcinoma arising from Barrett's esophagus: the first reported case in the esophagus.

Goblet cell adenocarcinoma (GCA) is a rare and distinctive amphicrine tumor comprised of goblet-like mucinous cells and neuroendocrine cells. It is believed to originate from pluripotent stem cells located at the base of crypts. GCA predominantly arises from the appendix, with a few reported cases in extra-appendiceal locations such as the colorectum, small intestine, and stomach. In this case report, we present a unique instance of a 64-year-old male who initially received a diagnosis of neuroendocrine carcinoma in the distal esophagus based on biopsy but, following resection, was subsequently re-diagnosed with GCA arising from Barrett's esophagus.

Appendiceal goblet cell adenocarcinoma newly classified by WHO 5th edition: a case report (a secondary publication).

BACKGROUND: Appendiceal goblet cell adenocarcinoma (AGCA) is a newly proposed cancer type in the 5th edition of the WHO Classification of Tumours in 2019. We experienced this rare form of appendiceal primary neoplasm. CASE PRESENTATION: An 85-year-old male presented a positive fecal occult blood test. A series of imagings revealed a type 1 tumor, located on the appendiceal orifice. The subsequent biopsy made the diagnosis of signet-ring cell carcinoma. Consequently, he underwent the laparoscopic-assisted ileocecal resection. Initially, the tumor was suspected to be a Goblet cell carcinoid (GCC). There was a discrepancy between the histological and immunostaining findings: the tumor cells exhibited morphological similarities to GCCs, however displayed limited staining upon immunostaining. Ultimately, we concluded that the tumor should be classified as AGCA, by following WHO 5th Edition. AGCA represents a newly categorized subtype of adenocarcinomas. Because of our preoperative suspicion of malignancy, we performed tumor resection with regional lymph node dissection, despite the fact that most appendiceal malignant tumors are typically identified after an appendectomy. CONCLUSION: We experienced a case that provides valuable insights into the comprehension of AGCA, a recently established pathological entity in the WHO 5th Edition. This article is an acceptable secondary publication of a case report that appeared in Azuma et al. (J Jpn Surg Assoc 83:1103-1108, 2022).

Clinicopathological and molecular characterization of extra-appendix goblet cell adenocarcinomas.

Goblet cell adenocarcinoma (GCA) is a distinctive type of endocrine-exocrine mixed tumor, exhibiting intermediate morphological features between neuroendocrine tumor and adenocarcinoma. It predominantly arises in the appendix, but primary extra-appendiceal GCA is extremely rare. Here, we presented six cases of primary extra-appendiceal GCA from 2016 to 2022. Notably, one case was originating in the bladder which was the first report of primary GCA to occur outside the digestive tract. The tumors frequently displayed variable goblet cell morphology, characterized by cytoplasmic mucin accumulation and basally located nucleus. Low-grade components typically exhibited glandular or clustered patterns without prominent fibrotic responses. High-grade components demonstrated cribriform, cluster and single-file arrangement accompanied by marked fibrous reactions. Immunohistochemically, the tumors showed positivity for both neuroendocrine markers（synaptophysin, chromogranin A, CD56 ）and adenoids markers（CDX-2, CK20）. Next-generation sequencing revealed the most prevalent mutated genes within GCAs were TP53. Due to their morphological and immunohistochemical similarities to primary appendiceal GCA counterparts, we propose a distinct category for extra-appendiceal Goblet cell adenocarcinoma.

Appendiceal goblet cell adenocarcinoma with perineural invasion extending into the ileocecal lesion.

BACKGROUND: Appendiceal goblet cell adenocarcinoma (GCA) is a rare subtype of primary appendiceal adenocarcinoma with an incidence of 1-5 per 10,000,000 people per year. Appendiceal tumors are often diagnosed after appendectomy for acute appendicitis. Notably, however, there is currently no standard treatment strategy for GCA, including additional resection. We report a case of appendiceal GCA with perineural extension into the cecum, in which ileal resection was considered effective. CASE PRESENTATION: A 41-year-old man was diagnosed with acute appendicitis and underwent appendectomy. Histopathological findings revealed GCA (T3, Pn1). He was referred to our hospital for additional resection. Preoperative examination indicated a diagnosis of GCA cT3N0M0. Laparoscopic ileocecal resection and D3 lymph node dissection were performed 2 months after initial appendectomy. The patient had a good postoperative course and was discharged 8 days after surgery. Histopathological findings showed a GCA invading the cecum, despite an intact appendiceal stump, no lymph node metastasis, no vascular invasion, and no horizontal extension into the submucosa. Direct invasion of the tumor through the serosa was not observed, but perineural extension was conspicuous in the cecum, suggesting that the GCA extended into the cecum via perineural invasion. The resection margins were negative. The patient has survived free of recurrence for a year after ileocecal resection. CONCLUSIONS: The current patient was diagnosed with appendiceal GCA following appendectomy for acute appendicitis. Despite intact of appendiceal stump and no evidence of lymph node or distant metastasis, he underwent laparoscopic ileocecal resection and D3 lymph node dissection 2 months after initial appendectomy, with a favorable outcome. Despite the detection of perineural invasion, the patient declined adjuvant therapy. This case suggests that extensive resection may be required in patients with appendiceal GCA, but the role of adjuvant therapy remains unclear.

GLP-1R signaling modulates colonic energy metabolism, goblet cell number and survival in the absence of gut microbiota.

OBJECTIVES: Gut microbiota increases energy availability through fermentation of dietary fibers to short-chain fatty acids in conventionally raised mice. Energy deficiency in germ-free (GF) mice increases glucagon-like peptide-1 (GLP-1) levels, which slows intestinal transit. To further analyze the role of GLP-1-mediated signaling in this model of energy deficiency, we re-derived mice lacking GLP-1 receptor (GLP-1R KO) as GF. METHODS: GLP-1R KO mice were rederived as GF through hysterectomy and monitored for 30 weeks. Mice were subjected to rescue experiments either through feeding an energy-rich diet or colonization with a normal cecal microbiota. Histology and intestinal function were assessed at different ages. Intestinal organoids were assessed to investigate stemness. RESULTS: Unexpectedly, 25% of GF GLP-1R KO mice died before 20 weeks of age, associated with enlarged ceca, increased cecal water content, increased colonic expression of apical ion transporters, reduced number of goblet cells and loss of colonic epithelial integrity. Colonocytes from GLP-1R KO mice were energy-deprived and exhibited increased ER-stress; mitochondrial fragmentation, increased oxygen levels and loss of stemness. Restoring colonic energy levels either by feeding a Western-style diet or colonization with a normal gut microbiota normalized gut phenotypes and prevented lethality. CONCLUSIONS: Our findings reveal a heretofore unrecognized role for GLP-1R signaling in the maintenance of colonic physiology and survival during energy deprivation.

A novel function of benzoic acid to enhance intestinal barrier defense against PEDV infection in Piglets.

The intestinal barrier of newborn piglets is vulnerable and underdeveloped, making them susceptible to enteric virus infections. Benzoic acid (BA), employed as a growth promoter, exhibits the potential to enhance the gut health of piglets by modulating intestinal morphometry and tight junction dynamics. However, the extent to which BA regulates the intestinal mucus barrier through its impact on stem cells remains inadequately elucidated. Therefore, this study was conducted to investigate the effects of BA on the intestinal barrier and the differentiation of intestinal stem cells, employing in vivo piglet and in vitro intestinal organoid models. Our investigation revealed a significant increase in the number of goblet cells within the small intestine, as well as the strengthening of the mucus barrier in vivo following oral treatment with BA, providing partial protection against PEDV infection in piglets. Additionally, in vitro cultivation of enteroids with BA led to a notable increase in the number of MUC2+ GCs, indicating the promotion of GC differentiation by BA. Furthermore, transcriptome analysis revealed an upregulation of the number of GCs and the expression of cell vesicle transport-related genes during BA stimulation, accompanied by the downregulation of the Wnt and Notch signaling pathways. Mechanistically, MCT1 facilitated the transport of BA, subsequently activating the MAPK pathway to mediate GC differentiation. Overall, this study highlights a novel function for BA as a feed additive in enhancing the intestinal mucus barrier by promoting intestinal GC differentiation, and further prevents viral infection in piglets.

Cassia alata's dual role in modulating MUC2 expression in Eimeria papillata-infected jejunum and assessing its anti-inflammatory effects.

Coccidiosis poses significant hazards to animals, particularly in terms of compromised health, reduced productivity, and economic losses in livestock farming. The conventional treatments for coccidiosis often involve synthetic drugs, contributing to concerns about drug resistance and environmental impact. The pressing need for eco-friendly alternatives is highlighted in this study, emphasizing the importance of exploring medicinal plants like Cassia alata leaf extracts (CAE) against Eimeria papillata-induced infection in mice. The CAE exhibited significant phenolic (2.17 ± 0.03 g/100 g) and flavonoid (0.14 ± 0.01 g/100 g) content and demonstrated notable antioxidant activity. In infected mice, the CAE treatment led to a substantial reduction in oocyst output (~6 fold), ameliorating necrotic enteritis and inflammatory changes in the jejunum. Additionally, CAE treatment increased goblet cell numbers (9.3 ± 0.1 / villus) and decreased macrophage infiltration in the intestinal villi. Molecular analyses revealed CAE's positive modulation of MUC2 gene and notably reduced the levels of pro-inflammatory cytokines (specifically IL-1ß, IL-10, and IFN-γ) when contrasted with the infected cohort. Furthermore, CAE treatment significantly reduced nitric oxide levels (44.03 ± 2.4 µmol/mg), showcasing its anti-inflammatory properties. The findings of this study not only contribute to the understanding of CAE's therapeutic potential but also underscore the importance of seeking eco-friendly alternatives in the face of coccidiosis challenges, addressing both the well-being of animals and the sustainability of agricultural practices. RESEARCH HIGHLIGHTS: Cassia alata extract (CAE) exhibited significant phenolic and flavonoid content, displaying notable antioxidant activity. In infected mice, CAE treatment led to a substantial reduction in oocyst output, ameliorating necrotic enteritis and inflammatory changes in the jejunum. CAE treatment increased goblet cell numbers and decreased macrophage infiltration in the intestinal villi, while molecular analyses revealed its positive modulation of the MUC2 gene and notable reduction in pro-inflammatory cytokine levels. Additionally, CAE treatment significantly reduced nitric oxide levels, showcasing its anti-inflammatory properties.

Peritoneal dissemination of appendiceal goblet cell adenocarcinoma mimicking white pus caused by peritonitis following appendicitis: an instructive case report.

BACKGROUND: Goblet cell adenocarcinoma is an extremely rare tumor in which the same cells exhibit both mucinous and neuroendocrine differentiation. It is considered more aggressive compared to conventional carcinoids and more likely to cause metastasis. CASE PRESENTATION: We report a case of goblet cell adenocarcinoma with peritoneal metastases. A 62-year-old man underwent appendectomy for acute appendicitis. Intraoperatively, inflammatory white pus and a small amount of dirty ascites were observed in the lower abdomen with severely inflamed appendix. Histopathological examination of the specimen collected during appendectomy revealed goblet cell adenocarcinoma with a positive surgical margin. One month later, additional ileal resection was planned. Laparoscopic examination revealed disseminated nodules throughout the abdominal cavity. Therefore, the patient underwent resection of the peritoneal nodules. The peritoneal specimens confirmed the histopathological findings. Thus we diagnosed the patient with peritoneal dissemination of appendiceal goblet cell adenocarcinoma. CONCLUSIONS: In cases wherein white pus is observed during surgery for acute appendicitis, considering the possibility of dissemination, collecting samples for histopathological examination, and initiating early treatment are crucial.

Effect of dietary Moringa oleifera on production performance and gut health in broilers.

Objective: In the present research work, we examined the dietary Moringa oleifera effect on gut health and growth traits in chickens. Materials and Methods: There were 280 chicks (day old) that were weighted and allotted uniformly in seven groupings, each containing eight replicates (n = 5). Birds were supplemented with M. oleifera leaf extract (MLE) and seed extract (MSE) for 35 days. Group I was the control (fed merely basal diets), while Group II received 0.8% MLE, Group III was given 0.8% MSE, Group IV was given 1.2% MLE, Group V was given 1.2% MSE, Group VI was given 0.8% MLE + 0.8% MSE, and Group VII was given 1.2% MLE + 1.2% MSE. At the end of the fifth week, two chickens were selected from each replica, and samples (small intestine and ileal ingesta) were collected. Results: The chicken diet with MLE and MSE supplements saw significant improvement (p < 0.05) in both feed conversion ratio (FCR) and body weight gain (BWG). In the small intestine (duodenal, jejunal, and ileal), dietary MLE and MSE supplements significantly increased (p < 0.05) the surface area of the villus and the ratio of their height/crypt depth in comparison to the control group. The MLE and MSE supplements significantly increased (p < 0.05) the total goblet cell counts in the small intestine. The Lactobacillus spp. count was significantly improved (p < 0.05) and reduced (p < 0.05) in Escherichia coli counts when the bird diet was supplemented with MLE (0.8%) and MSE (0.8%). Conclusion: Results indicated that M. oleifera leaf and seed extract diet improved the growth trait and gut health in chickens.

Right Hemicolectomy and Appendicectomy as Treatments for Goblet Cell Adenocarcinoma: A Comparative Analysis of Two Large National Databases.

INTRODUCTION: Right hemicolectomy (RHC) remains the treatment standard for goblet cell adenocarcinoma (GCA), despite limited evidence supporting survival benefit. This study aims to explore factors influencing surgical management and survival outcomes among patients treated with RHC or appendicectomy using NCRAS (UK) and SEER (USA) data. METHODS: A retrospective analysis was conducted using 998 (NCRAS) and 1703 (SEER) cases. Factors influencing procedure type were explored using logistic regression analyses. Overall survival (OS) probabilities and Kaplan-Meier (KM) plots were generated using KM analysis and the log-rank test compared survival between groups. Cox regression analyses were performed to assess hazard ratios. RESULTS: The NCRAS analysis revealed that age and regional stage disease were determinants of undergoing RHC, with all age groups showing similar odds of receiving RHC, excluding the 75+ age group. The SEER analysis revealed tumour size > 2 cm, and receipt of chemotherapy were determinants of undergoing RHC, unlike the distant stage, which was associated with appendicectomy. Surgery type was not a significant predictor of OS in both analyses. In NCRAS, age and stage were significant predictors of OS. In SEER, age, stage, and Black race were significant predictors of worse OS. CONCLUSIONS: The study shows variations in the surgical management of GCA, with limited evidence to support a widespread recommendation for RHC.

Chlorella alleviates the intestinal damage of tilapia caused by microplastics.

Polyethylene microplastics (MPs) of the different sizes may result in different response in fish. Studies showed microorganisms adhered to the surface of MPs have toxicological effect. Juveniles tilapia (Oreochromis niloticus, n = 600, 26.5 ± 0.6 g) were dispersed into six groups: the control group (A), 75 nm MP exposed group (B), 7.5 µm group (C) and 750 (D) µm group, 75 nm + 7.5 µm+750 µm group (E) and 75 nm + Chlorella vulgaris group (F), and exposed for 10 and 14 days. The intestinal histopathological change, enzymic activities, and the integrated "omics" workflows containing transcriptomics, proteomics, microbiota and metabolomes, have been performed in tilapia. Results showed that MPs were distributed on the surface of goblet cells, Chlorella group had severe villi fusion without something like intestinal damage, as in other MPs groups. The intestinal Total Cholesterol (TC, together with group E) and Tumor Necrosis Factor α (TNFα, except for group B) contents in group F were significantly increased, cytochrome p450 1a1 (EROD, group B and E) significantly increased, adenosine triphosphate (ATP), lipoprotein lipase (LPL) and caspase 3 (except group B) also significantly increased at 14 d. At 14 days, group E saw considerably higher regulation of the actin cytoskeleton, focal adhesion, insulin signaling pathway, and AGE-RAGE signaling pathway in diabetes complications. Whereas, chlorella enhanced the focal adhesion, cytokine-cytokine receptor interaction, and MAPK signaling pathways. PPAR signaling pathway has been extremely significantly enriched via the proteomics method. Candidatus latescibacteria, C. uhrbacteria, C. abyssubacteria, C. cryosericota significantly decreased caused by MPs of different particle sizes. Carboxylic acids and derivatives, indoles and derivatives, organooxygen compounds, fatty acyls and organooxygen compounds significantly increased with long-term duration, especially PPAR signaling pathway. MPs had a size-dependent long-term effect on histopathological change, gene and protein expression, and gut microbial metabolites, while chlorella alleviates the intestinal histopathological damage via the integrated "omics" workflows.

Case report: A rare case of coexistence of low-grade appendiceal mucinous neoplasia and goblet cell adenocarcinoma in the appendix.

Background: Primary appendiceal tumors are rare. Low-grade appendiceal mucinous neoplasia (LAMN) and goblet cell adenocarcinoma (GCA) account for 20% and 14% of primary appendiceal tumors, respectively. The coexistence of LAMN and GCA is an extremely rare event. This report presents a case of an elderly male patient with an appendiceal tumor composed of LAMN and GCA in the same appendix. Case presentation: A 72-year-old male patient was admitted to our institution presenting with a history of abdominal pain localized to the right lower quadrant for two months. Abdominal computed tomography (CT) showed a large dilated thickened cystic mass in the appendix, along with a small duodenal diverticulum. Laboratory tests indicated elevated levels of serum carcinoembryonic antigen (CEA) and cancer antigen 199 (CA19-9) markers. The patient underwent a laparoscopic right hemicolectomy and exploration of the duodenal diverticulum, and there was no finding of perforation of the duodenal diverticulum. Focal positivity for chromogranin A (CgA) and synaptophysin (Syn) was observed in the tumor cells of GCA. The final pathological diagnosis revealed the coexistence of LAMN staged pT4a and grade 1 GCA staged pT3 in the appendix. Unfortunately, the patient died due to severe septic shock and circulatory failure secondary to a perforated duodenal diverticulum. Conclusions: The coexistence of LAMN and GCA are extremely rare in the appendix and may result from the proliferation of two independent cellular lines. The coexistence of distinct neoplasms poses diagnostic and management challenges. Multidisciplinary team discussion may be essential in the effective management of these patients.