MUC1 Expression Research Articles

YAP1::KMT2A-rearranged sarcomas harbor a unique methylation profile and are distinct from sclerosing epithelioid fibrosarcoma and low-grade fibromyxoid sarcoma.

Sclerosing epithelioid fibrosarcoma (SEF) was originally described as a peculiar variant of fibrosarcoma in 1995. Subsequent studies showed that conventional SEF was associated with both immunohistochemical expression of MUC4 and EWSR1/FUS gene rearrangements with CREB3L1 as the predominant fusion partner. Since then, a distinct group of fibrous tumors characterized by YAP1::KMT2A and KMT2A::YAP1 gene rearrangements and SEF-like morphology has been described. These YAP1::KMT2A-rearranged sarcomas were further shown to lack both immunohistochemical expression of MUC4 and canonical EWSR1/FUS gene rearrangements. To better understand whether the YAP1::KMT2A-rearranged sarcomas represent a subset of MUC4-negative SEF or a distinct entity, we studied 22 cases of YAP1::KMT2A-rearranged sarcomas, the largest series to date, and performed a literature review of all previously reported next-generation sequencing (NGS)-confirmed cases. These sarcomas often arose in young adults with a median age of 38 years and a male to female (M:F) ratio of 1.4:1. They predominantly involved somatic soft tissue; however, we report the first case of a tumor that primarily developed inside bone. Immunohistochemical studies showed that the tumors often demonstrated expression of YAP1 and EMA, while all tested cases were negative for MUC4. NGS confirmed the presence of YAP1::KMT2A gene fusions in all cases, some of which initially had false negative results with targeted FISH and solid tumor panel testing. Clinical follow-up information was available in 14 patients with a median follow-up of 25 months (range 1 to 170 months). Local recurrence occurred in three patients (21%) and metastasis developed in seven patients (50%). DNA methylation analysis further showed that YAP1::KMT2A-rearranged sarcomas formed a distinct cluster, which was clearly separate from both conventional SEF and low-grade fibromyxoid sarcoma (LGFMS). These results suggest that YAP1::KMT2A-rearranged sarcomas likely represent a unique sarcoma subtype with propensity for aggressive behavior.

Amelioration of inflammatory bowel disease by Bifidobacterium animalis subsp. lactis XLTG11 in combination with mesalazine.

The treatment of inflammatory bowel disease (IBD) remains challenging and significantly impacts both patients and their families. This study evaluated the role of Bifidobacterium animalis subsp. lacti XLTG11 (XLTG11) in combination with mesalazine (5-ASA) in the improvement of IBD. The results demonstrated that the XLTG11+5-ASA group exhibited superior recovery compared to both the XLTG11-only group and the 5-ASA-only group. The XLTG11+5-ASA group significantly reduced myeloperoxidase activity (MPO), attenuated colonic tissue damage, lowered the levels of lipopolysaccharides (LPS) and D-lactic acid (D-LA), and decreased intestinal permeability. Furthermore, it upregulated the mRNA expression of Claudin-1, Occludin, ZO-1, and MUC2, which contributed to the protective effect on intestinal barrier function. Additionally, the XLTG11+5-ASA group significantly increased the levels of anti-inflammatory cytokines while decreasing pro-inflammatory cytokine levels. Notably, treatment with the XLTG11+5-ASA group significantly increased levels of acetic, propionic, and butyric acids, as well as the relative abundance of beneficial bacteria such as Bifidobacterium and Lactobacillus, while decreasing the relative abundance of Enterococcus, Enterobacteriaceae, and Clostridium perfringens. The results indicate that the combination of XLTG11 and 5-ASA was more effective in treating IBD than either treatment alone, significantly improving IBD-related symptoms and providing a scientific basis for future clinical applications.

Postbiotic Effect of Escherichia coli CEC15 and Escherichia coli Nissle 1917 on a Murine Model of 5-FU-induced Intestinal Mucositis.

Probiotics are live microorganisms that, when administered in adequate amounts, can bring health benefits to the host. Most of these organisms are found naturally in the human gastrointestinal tract. Escherichia coli strains Nissle 1917 (EcN), and CEC15 have shown beneficial effects in murine models of intestinal inflammation, such as colitis and mucositis. The present study evaluated the effects as postbiotic of heat-inactivated and cell-free supernatant preparations of EcN and CEC15 in attenuating 5-fluorouracil (5-FU)-induced intestinal mucositis in mice and compared them with the probiotic effects of the live preparations. BALB/c mice were fed, by daily gavage, with 1010 CFU of live or inactivated bacteria or with 300 µL of cell-free supernatant for 12 days. On the 10th day, all animals, except for the control group, received an intraperitoneal injection of 5-FU (300mg/kg). After 72h of 5-FU administration, animals were euthanized, and the ileum and blood were collected for analysis. Treatments with live and heat-inactivated CEC15 mitigated weight loss, preserved intestinal length, reduced histological damage, maintained goblet cells, decreased neutrophil infiltration, and modulated expression of inflammatory and barrier genes when compared to 5-FU mucositis controls. EcN showed more limited effects. CEC15 upregulated mRNA expression of the mucin MUC2 and tight junction protein TJP1. CEC15 demonstrated protective effects against 5-FU-induced mucositis, whether administered with live, heat-inactivated, or cell-free supernatant. This suggests that CEC15 mediates a protective response via secreted metabolites and does not require viability. The postbiotic forms of CEC15 present advantages for use in immunocompromised patients. This study elucidates the anti-inflammatory and barrier-protective effects of CEC15 against intestinal mucositis.

Middle Ear microRNAs Drive Mucin Gene Response.

To investigate the role of microRNA-378 (miR-378) in the regulation of mucin gene expression and inflammatory response in human middle ear epithelial cells (HMEEC) during bacterial infection by non-typeable Haemophilus influenzae (NTHi). Human middle ear epithelial cells (HMEEC) were cultured and transfected with miR-378 or control miRNA. Post-transfection, cells were exposed to NTHi lysates. mRNA levels of MUC5B, MUC5AC, and IL-8 were quantified using RT-qPCR, and promoter activity was measured via luciferase assays. The effects of miR-378 on mucin and cytokine gene expression were analyzed. Transfection with miR-378 significantly increased the expression of MUC5B (3.6 fold, p < 0.01), MUC5AC (19.1 fold, p < 0.01), and IL-8 (2.01 fold, p < 0.05) in HMEEC. NTHi exposure reduced MUC5B (1.385 fold, p < 0.05) and MUC5AC (1.61 fold, p < 0.05) gene expression in miR-378 transfected cells but significantly increased IL-8 levels (1.32 fold, p < 0.05). Luciferase assays showed that miR-378 upregulated the promoter activity of MUC5B (1.4 fold, p < 0.01) and MUC5AC (1.6 fold, p < 0.01) genes, indicating its role in transcriptional regulation. miR-378 plays a crucial role in promoting mucin overproduction and an inflammatory response in the middle ear epithelium during OM. Targeting miR-378 could offer a novel therapeutic strategy for preventing the progression from AOM to COM. na Laryngoscope, 2024.

Differential expression of the SLC34A2 gene in different histological subtypes of ovarian carcinomas

BACKGROUND: Patients with ovarian carcinoma demonstrate different sensitivity to chemotherapy; therefore, to increase the effectiveness of treatment, it is necessary to take into account the characteristics of each patient's tumor, including the histological subtype. AIM: To search for new molecular markers of ovarian cancer by analyzing the expression of candidate genes, including BAX, SLC34A2, MUC16, CD300A, and XKR8, in ovarian carcinomas of different histological subtypes. MATERIAL AND METHODS: Analysis of the expression of the BAX, SLC34A2, MUC16, CD300A, and XKR8 genes in 33 carcinomas taking into account their histological subtypes was performed using real-time polymerase chain reaction. Tumor samples from patients with ovarian carcinoma were obtained from the Blokhin National Medical Research Center of Oncology (Moscow) and the Republican Clinical Oncology Dispensary (Kazan) and divided into groups by histological subtypes: serous of high (n=16) and low (n=6) grade malignancy, endometrioid (n=8) and mucinous (n=3). Additional analysis was performed using microarray data from the Gene Expression Omnibus open database to determine the expression of selected candidate genes in ovarian carcinomas of different histological subtypes. The dataset included 4 normal ovary samples and 95 ovarian carcinoma samples of different histological subtypes: serous (n=41), endometrioid (n=37), and mucinous (n=13). Statistical analysis of the data was performed using Prism software. Nonparametric Dunn's test was used to compare gene expression in several patient groups. RESULTS: The expression level of the SLC34A2 gene was increased in low-grade serous carcinomas (p=0.0257) compared to mucinous carcinomas. Using bioinformatics analysis, we found increased expression of the SLC34A2 gene in serous (p=0.0023) and endometrioid ovarian carcinomas (p=0.0355) compared to normal ovarian tissues. CONCLUSION: The SLC34A2 gene can be considered as a potential molecular marker for differential diagnosis of ovarian cancer histological subtypes and a target for therapy of patients with low-grade serous ovarian carcinoma.

Live Multi-Strain Probiotics Enhance Growth Performance by Regulating Intestinal Morphology and Microbiome Population in Weaning Piglets.

The effects of different forms of multi-strain probiotics on weaning piglets are limitedly addressed. Thus, this study investigated the effects of live or inanimate multi-strain probiotics comprising Lactobacillus plantarum, Streptococcus thermophilus, and Bacillus subtilis on growth performance, intestinal morphology, fecal microbiota, short-chain fatty acids, and intestinal gene expression of weaning piglets. A total of 160 weaning piglets (4 weeks old) were randomly allocated into four treatments (CON: basal diet; AB: basal diet with 110 ppm and 66 ppm colistin in the weaning and nursery phases, respectively; LP: basal diet with 2.0 × 109 CFU/kg live probiotics; and IP: basal diet with 2.0 × 109 CFU/kg inanimate probiotics). Piglets fed with LP had significantly lower FCR compared to those of the CON and IP groups in week 4 to week 8 (p < 0.05). Moreover, the LP group had significantly higher villus height (VH) compared with AB at week 6, lower crypt depth (CD) compared with IP, and higher VH/CD ratio compared to other treatments at week 10 (p < 0.05), which indicate healthier intestinal morphology. Probiotic treatments (LP and IP) increased Bifidobacterium population compared to CON at week 6 and lowered Enterobacteriaceae at week 6 and week 10 (p < 0.05). Regarding gene expressions of intestinal integrity, LP showed significantly higher TFF3 expression compared with CON and AB at week 6 and compared with other treatments in jejunum at week 10 (p < 0.05). IP treatment had significantly higher MUC2 expression compared to other treatments at week 6 and week 10 (p < 0.05). Overall, live multi-strain probiotics improved growth efficiency by enhancing gut integrity and microbiome balance, making them a potential antibiotic alternative to ameliorate weaning stress and promote productive performance in weaning piglets.

Euphorbium compositum SN improves the innate defenses of the airway mucosal barrier network during rhinovirus infection

BackgroundRhinoviruses (RV) are the major cause of common colds in healthy individuals and are associated with acute exacerbations in patients with chronic lung diseases. Yet, no vaccines or effective treatment against RV are available. This study investigated the effect of Euphorbium compositum SN (ECSN6), a multicomponent, multitarget medication made from natural ingredients, on the mucosal barrier network during RV infection.MethodsMucociliary-differentiated airway epithelial cell cultures were infected with RV or sham, and treated with 20% ECSN6 or placebo twice daily. Barrier integrity was assessed by measuring transepithelial resistance (TER), permeability to inulin, and expression and localization of intercellular junctions proteins (IJ). Ciliary beat frequency (CBF), expression of pro-inflammatory cytokines, antiviral interferons and mucins, and viral load were also measured. C57BL/6 mice were infected intranasally with RV or sham and treated with 40% ECSN6 or placebo twice daily. Inflammation of sinunasal mucosa, localization of E-cadherin, viral load and mucin gene expression were determined.ResultsECSN6-treated, uninfected cell cultures showed small, but significant increase in TER over placebo, which was associated with enhanced localization of E-cadherin and ZO-1 to IJ. In RV-infected cultures, treatment with ECSN6, but not placebo prevented RV-induced (1) reduction in TER, (2) dissociation of E-cadherin and ZO-1 from the IJ, (3) mucin expression, and (4) CBF attenuation. ECSN6 also decreased RV-stimulated expression of pro-inflammatory cytokines and permeability to inulin. Although ECSN6 significantly increased the expression of some antiviral type I and type III interferons, it did not alter viral load. In vivo, ECSN6 reduced RV-A1-induced moderate inflammation of nasal mucosa, beneficially affected RV-A1-induced cytokine responses and Muc5ac mRNA expression and prevented RV-caused dissociation of E-cadherin from the IJ of nasal mucosa without an effect on viral clearance.ConclusionsECSN6 prevents RV-induced airway mucosal barrier dysfunction and improves the immunological and mucociliary barrier function. ECSN6 may maintain integrity of barrier function by promoting localization of tight and adherence junction proteins to the IJ. This in turn may lead to the observed decrease in RV-induced pro-inflammatory responses in vitro. By improving the innate defenses of the airway mucosal barrier network, ECSN6 may alleviate respiratory symptoms caused by RV infections.

SLC41A1 overexpression correlates with immune cell infiltration in HCC and promotes its malignant progression.

Solute carrier 41 (SLC41) has been identified as a family of magnesium (Mg2+) transporters that participate in various diseases, including tumor development and progression. Recent studies revealed SLC41A3 acted as an oncogene and predicted poor survival for hepatocellular carcinoma (HCC) patients. However, the potential function of SLC41A1 in HCC remains unclear. In our study, we focused on the levels and putative mechanisms of SLC41A1 in HCC. Using bioinformatics techniques, we found SLC41A1 was upregulated in HCC, which was verified by immunostaining of HCC patients. SLC41A1 was correlated with clinicopathological characteristics, and could be utilized as independently diagnostic and prognostic markers for HCC. By exploring MethSurv website, DNA methylation was identified in SLC41A1, and several methylated CpG sites might affect overall survival of HCC patients. Using Gene Ontology (GO) , Kyoto Encyclopedia of Genes and Genomes (KEGG), gene set enrichment analysis (GSEA), protein-protein interaction (PPI) network, we found SLC41A1 overexpression was related to several tumor-promoting pathways and molecules, such as degradation of extracellular matrix, cell adhesion and O-linked glycosylation, and expression of CXCL1, CXCL5 and MUC1. The results of single-sample GSEA (ssGSEA) showed SLC41A1 might regulate infiltration of multiple immune cells, resulting in the imbalance between immune suppression and immune surveillance. Cellular experiments showed that knockdown of SLC41A1 inhibited proliferation, migration and invasion of HCC, whereas SLC41A1 overexpression exerted the tumor-promoting effects. Collectively, our results shed light on new insights into expression, putative roles and mechanisms of SLC41A1 in HCC, providing novel diagnostic biomarkers and therapeutic targets for HCC.

Effect of Matrine on growth performance, gut health, and gut microbiota in chickens infected with avian pathogenic Escherichia coli

Avian pathogenic Escherichia coli (APEC) is a major cause of avian colibacillosis. Matrine, a natural component derived from Sophora flavescens, exhibits various pharmacological effects, including anti-inflammatory and antioxidant activities. However, its role in mitigating APEC-induced intestinal damage in chickens remains insufficiently understood. This study aimed to explore the protective effects and potential mechanisms of matrine against APEC-induced intestinal damage. Chickens were administered matrine (10 or 20 mg/kg) from 6 days old for 5 days, followed by an APEC intraperitoneal injection on day 10. After 72 h of APEC infection, tissues were collected for analysis. Results indicated that pretreatment with matrine alleviated the symptoms of APEC infection in chickens, improving survival rates and promoting weight gain. Additionally, pretreatment with matrine reduced the secretion and gene expression of IL-1β, IL-6, and TNF-α in intestinal tissues, while enhancing serum SOD, GSH, and CAT activity, as well as gene expression levels in the intestine. Pretreatment with matrine reduced the levels of TLR4, MyD88, and NF-κB in intestinal tissues. Moreover, pretreatment with matrine ameliorated intestinal inflammation and pathological damage, restoring the expression of ZO-1, Occludin, and MUC2 in the intestine during APEC infection. Furthermore, pretreatment with matrine alleviated gut microbiota dysbiosis by lowering the abundance of harmful bacteria. In summary, matrine alleviated APEC-induced intestinal inflammation and damage, potentially by inhibiting NF-κB signaling pathway and reshaping the gut microbiota. These findings provide promising insights into the prevention and treatment of avian colibacillosis.

AKK-derived outer membrane vesicles alleviate indomethacin-induced mucin secretion reduction in LS174T cells by inhibiting endoplasmic reticulum stress.

AKK-derived outer membrane vesicles (AKK-OMVs) have shown potential in modulating intestinal mucosal immunity by increasing the number of intestinal goblet cells. However, it remains unclear whether AKK-OMVs can directly regulate MUC2 secretion in goblet cells exposed to indomethacin in vitro and the underlying mechanisms involved. The abnormal mucin secretion model in LS174T cells was established using indomethacin, with treatment including Akkermansia muciniphila (AKK) supernatant, AKK-OMVs, and extracellular vesicle removal supernatant. The effects of these treatment on MUC2 expression were observed. Transcriptomic sequencing analysis was used to explore the underlying regulatory mechanisms, which were further validated through qRT-PCR and western blotting. The treatment with AKK supernatant and AKK-OMVs alleviated the indomethacin-induced reduction in MUC2 secretion in goblet cells. Mechanistically, transcriptomic analysis showed that the gene expression associated with endoplasmic reticulum (ER) stress were upregulated after indomethacin treatment in LS174T cells. This suggests that AKK-OMVs, as the active component in the supernatant, improved MUC2 expression by inhibiting ER stress. AKK-OMVs can directly stimulate goblet cells to promote MUC2 secretion, providing potential for further in vivo studies to confirm their protective effects against indomethacin-induced intestinal injury.

Pulmonary-delivered Anticalin Jagged-1 antagonists reduce experimental airway mucus hyperproduction and obstruction.

Mucus hypersecretion and mucus obstruction are pathogenic features in many chronic lung diseases directly linked to disease severity, exacerbation, progression, and mortality. The Jagged-1/Notch pathway is a promising therapeutic target that regulates secretory and ciliated cell trans-differentiation in the lung. However, the Notch pathway is also required in various other organs. Hence, pulmonary delivery of therapeutic agents is a promising approach to target this pathway while minimizing systemic exposure. Using Anticalin® technology, Jagged-1 Anticalin binding proteins were generated and engineered to potent and selective inhalable Jagged-1 antagonists. Their therapeutic potential to reduce airway mucus hyperproduction and obstruction was investigated ex vivo and in vivo. In primary airway cell cultures grown at air-liquid interface and stimulated with inflammatory cytokines, Jagged-1 Anticalin binding proteins reduced both mucin gene expression and mucous cell metaplasia. In vivo, prophylactic and therapeutic treatment with a pulmonary-delivered Jagged-1 Anticalin binding protein reduced mucous cell metaplasia, epithelial thickening and airway mucus hyperproduction in IL-13 and house dust mite allergen-challenged mice, respectively. Further, in a transgenic mouse model with pathophysiologic features of cystic fibrosis and COPD, pulmonary-delivered Jagged-1 Anticalin binding protein reduced hallmarks of airway mucus obstruction. In all in vivo models a reduction of mucous cells with a concomitant increase of ciliated cells was observed. Collectively, these findings support Jagged-1 antagonists' therapeutic potential for patients with muco-obstructive lung diseases, and the feasibility of targeting the Jagged-1/Notch pathway by inhalation.

Detection of circulating tumor cells in women with early breast cancer

There are multiple methods and biomarkers with different detection rates to circulating tumor cells (CTCs) in women with breast cancer (BC). However, to the best our knowledge, no study has been carried out to detect CTCs in women with early BC in Mexico. Calculate the detection rate of CTCs in peripheral blood of Mexican women with early BC by quantification of the relative expression of KRT19, MUC1 and SCGB2A2. Observational, longitudinal, analytical study, which included 62 Mexican women, over 18 years of age, with BC clinical stage 0, I and II. Cells with a density < 1.077 g/ml were isolated from 4 mL of peripheral blood obtained 24 h before surgery, RNAS was extracted and RT-qPCR was performed to quantify the relative expression of KRT19, MUC1 and SCGB2A2. The diagnosis of BC was confirmed in the definitive pathological study in 59 women. 1 case (1.7%), expressed KRT19, 18 cases (30.5%) MUC1, 2 cases (3.4%) SCGB2A2, and 19 cases (32.2%) expressed at least one of the three biomarkers. CTCs detection rates were like those reported in other populations when MUC1 was used, but lower when KRT19 and SCGB2A2 were used. Standardization of blood sample collection and processing, as well as biomarker expression analysis, is important to reduce variability in the detection of CTCs in specific populations.

Mucin gene expression in the large intestine of young pigs: the effect of dietary level of two types of chicory inulin

Mucin gene expression in the large intestine of young pigs: the effect of dietary level of two types of chicory inulin

Establishment and Characterization of Patient-Derived Intestinal Organoids from Pediatric Crohn's Disease Patients.

This study aimed to establish and characterize patient-derived intestinal organoids (PDOs) from children with Crohn's disease (CD). To generate PDOs, endoscopic biopsy specimens were obtained from non-inflamed duodenal bulbs of normal controls and CD patients. To verify the presence of PDOs, histological staining and quantitative reverse transcription polymerase chain reaction (RT-qPCR) analyses were performed. PDOs were successfully established in normal controls (n=2) and CD patients (n=2). Hematoxylin and eosin staining of formalin-fixed, paraffin-embedded PDO sections revealed crypt and villus structures, whereas immunofluorescence staining with EpCAM and DAPI confirmed the epithelial-specific architecture of the PDOs. RT-qPCR results revealed a significant increase in Lgr5, Si, and Chga gene expression and a decrease in Olfm4 and Muc2 expression in CD patients compared to normal controls, suggesting altered stem cell activity and mucosal barrier function (p<0.05). We successfully established and characterized PDOs in children with CD, providing a valuable tool for understanding the pathophysiology of the disease and evaluating potential therapeutic approaches. The differential gene expression of PDOs in CD patients might be caused by the complex interplay between epithelial adaptation and inflammation in the intestinal epithelium.

Liposome encapsulating pine bark extract in Nile tilapia: Targeting interrelated immune and antioxidant defense to combat coinfection with Aeromonas hydrophila and Enterococcus faecalis

Application of smart delivery systems for encapsulation of natural ingredients provides novel avenues and is being frequently developed. Thus, we aimed to highlight the effects of cyclosome liposomal pine bark extract (CL-PBE) on Nile tilapia growth, immunomodulation, antioxidant capacity and resistance against coinfection with Aeromonas hydrophila and Enterococcus faecalis and their associated virulence genes. The experiment was conducted on four fish groups receiving a control diet (control) along with three baseline meals supplemented with 200, 400 and 600 mg/kg diet of CL-PBE (CL-PBE 200, 400 and 600, respectively). At the end of the 12-weeks feeding trial, the tilapias were intraperitoneally challenged with virulent A. hydrophila strain and five days later, E. faecalis challenge was carried out. The results revealed that tilapias fed diets fortified with CL-PBE displayed significantly enhanced growth rate and feed conversion ratio in a dose-dependent manner. Moreover, we demonstrated that CL-PBE had potent antioxidant property presented by modulation of several markers of oxidative stress; substantial reductions in reactive oxygen species, hydrogen peroxide and malondialdehyde levels, an elevation in total antioxidant capacity and boosting glutathione peroxidase (GSH-Px), catalase (CAT) and superoxide dismutase (SOD) activities in fish serum and muscle tissues. This was also correlated with augmenting the expression of CAT, SOD, GSH-Px, Nrf2 and caspase-1 genes alongside reducing those of COX-2, HSP70 and iNOS genes in response to CL-PBE. Our data demonstrated that CL-PBE fortification counteracted the overly pronounced inflammatory response-mediated induction of IL-1β, TNF-α, MHCII and TLR2 genes at the transcriptional levels post coinfection together with promotion in MUC2 and IL-10 genes expression. Notably, our findings displayed optimal well-functioning fish immune system post dietary supplementation of CL-PBE for the protection against coinfection with A. hydrophila and E. faecalis. This was evident from the decline of their counts and hence encompassing the capacity to reduce cumulative mortality percentage in conjunction with interference with their virulence via the significant downregulatory effects of CL-PBE on E. faecalis esp and gelE and A. hydrophila act and fla virulence genes. Taken together, our study strongly suggested dietary inclusion of CL-PBE for Nile tilapias with superior growth performance and significant economic benefits coupled with potent stimulatory effects on antioxidant capacity and immune response expediting our detailed understanding of how coinfection with A. hydrophila and E. faecalis was controlled.

Endoscopic and clinicopathological features of early gastric papillary adenocarcinoma.

Gastric papillary adenocarcinoma (GPA), a well-differentiated gastric adenocarcinoma, is associated with a worse prognosis compared to other differentiated gastric adenocarcinomas. Therefore, there is an urgent need to characterize its endoscopic manifestations for guiding biopsy site selection and achieving accurate diagnosis. From January 1, 2016, to December 31, 2022, the data of 46 cases of early gastric papillary adenocarcinoma (EGPA) and 183 cases of early gastric differentiated tubular adenocarcinoma (EGDTA) diagnosed via pathological examination following endoscopic submucosal dissection (ESD) at the Second Hospital of Shandong University were collected. Propensity score matching (PSM) was employed to match 92 EGDTA patients at a ratio of 1:2, serving as the control group. Differences between the two groups were analyzed using multivariable logistic regression. Lastly, the relationship between vessels within epithelial circle (VEC) structures in EGPA and the degree of malignancy was assessed. Compared with EGDTA, EGPA was more likely to infiltrate the submucosa, more frequently associated with poorly differentiated cancer components, and more prone to invading lymphatic and blood vessels. EGPA was primarily located in the lower stomach and manifested as a uniformly elevated pattern under endoscopy, while VEC structural positivity could be visualized under ME-NBI. Moreover, EGPA lesions had larger diameters and were characterized by high expression of gastric mucins, namely MUC5AC and MUC6. When EGPA infiltrated the submucosa or contained poorly differentiated cancer components, the VEC structures were smaller. The present study demonstrated that EGPA exhibits a higher degree of malignancy. Endoscopic findings of a raised lesion with a uniform color under endoscopy and the presence of VEC structures under ME-NBI suggest a high possibility of EGPA. Moreover, smaller VEC structures were associated with a higher degree of malignancy, which may assist in guiding the selection of biopsy sites under endoscopy.

Rifaximin alleviates intestinal barrier disruption and systemic inflammation via the PXR/NFκB/MLCK pathway and modulates intestinal Lachnospiraceae abundance in heat-stroke mice

Heatstroke is a critical condition with a high mortality rate and intestinal barrier dysfunction is a key factor in its progression to sepsis in some patients. This study aimed to explore the protective effects of rifaximin on the intestinal barrier in heat-stroke mice and the underlying mechanisms. A mouse model of heat stroke was established, followed by rifaximin intervention. Rifaximin significantly improved survival rates, reduced core body temperature, and alleviated intestinal tissue damage. Further mechanistic studies revealed that rifaximin restored heat stroke-induced damage to intestinal barrier function by upregulating the expression of the tight junction proteins, ZO-1 and occludin. Additionally, 16S rRNA sequencing showed that rifaximin significantly increased the abundance of Lachnospiraceae in the gut and enhanced short-chain fatty acid butyrate levels. In vitro experiment results revealed that butyrate promotes the expression of the intestinal epithelial cell protein MUC2, thereby strengthening the intestinal barrier. Rifaximin also activated the pregnane X receptor (PXR) signaling pathway and inhibited the NF-κB/MLCK signaling pathway, reducing the permeability of intestinal epithelial cells. This study demonstrated that rifaximin protects the intestinal barrier in mice with heat stroke through multiple pathways by modulating the gut microbiota, increasing butyrate production, and activating the PXR signaling pathway. These findings provide a new theoretical basis for the clinical application of rifaximin in heat stroke treatment.

MMP-1, MMP-2, MMP-9, TIMP-1, TIMP-2, MUC1 and CD29 Expression in Endometrial Polyps at Implantation Window Compared to Neighbouring Normal Endometrium

MMP-1, MMP-2, MMP-9, TIMP-1, TIMP-2, MUC1 and CD29 Expression in Endometrial Polyps at Implantation Window Compared to Neighbouring Normal Endometrium

Development of engineered IL-36γ-hypersecreting Lactococcus lactis to improve the intestinal environment

Interleukin (IL) 36 is a member of the IL-1-like proinflammatory cytokine family that has a protective role in mucosal immunity. We hypothesized that mucosal delivery of IL-36γ to the intestine would be a very effective way to prevent intestinal diseases. Here, we genetically engineered a lactic acid bacterium, Lactococcus lactis, to produce recombinant mouse IL-36γ (rmIL-36γ). Western blotting and enzyme-linked immunosorbent assay results showed that the engineered strain (NZ-IL36γ) produced and hypersecreted the designed rmIL-36γ in the presence of nisin, which induces the expression of the recombinant gene. We administered NZ-IL36γ to mice via oral gavage, and collected the ruminal contents and rectal tissues. Colony PCR using primers specific for NZ-IL36γ, and enzyme-linked immunosorbent assay to measure the rmIL-36γ concentrations of the ruminal contents showed that NZ-IL36γ colonized the mouse intestines and secreted rmIL-36γ. A microbiota analysis revealed increased abundances of bacteria of the genera Acetatifactor, Eubacterium, Monoglobus, and Roseburia in the mouse intestines. Real-time quantitative PCR of the whole colon showed increased Muc2 expression. An in vitro assay using murine colorectal epithelial cells and human colonic cells showed that purified rmIL-36γ promoted Muc2 gene expression. Taken together, these data suggest that NZ-IL36γ may be an effective and attractive tool for delivering rmIL-36γ to improve the intestinal environment.

Lactobacillus paracasei JY062 and its exopolysaccharide enhance the intestinal barrier through macrophage polarization and Th17/Treg cell balance

Ulcerative colitis (UC) is an immune-mediated intestinal disease without a comprehensive cure, and the alleviation of UC has become an urgent problem. The results showed that JY062 with its EPS group (JEC) alleviated the intestinal barrier damage caused by LPS. After JEC intervention on Caco-2 cells, resulted in upregulation of ZO-1, Claudin-1, Occludin and MUC2 transcript levels and decreased mRNA expression of Claudin-2 (p < 0.05). JEC effectively attenuated the inflammatory response in UC mice and restoration of immunoglobulin levels (IgG, IgM and IgA), which resulted in shortening and swelling of the colon, disappearance of goblet cells, infiltration of inflammatory cells and mucosal damage were alleviated in mice. Similarly, changes in the expression of MUC2 and tight junction proteins after JEC intervention also occurred in UC mice. Administration of JEC significantly inhibited the differentiation of pro-inflammatory Th17 cells in the thymus and peripheral blood, promoted the differentiation of CD4+ T cells to Treg cells, and effectively regulated DSS-induced macrophage imbalance, which was manifested by the polarization of pro-inflammatory M1 macrophages to anti-inflammatory M2 macrophages. This study clearly demonstrates that JEC could significantly prevent intestinal barrier on DSS-induced experimental colitis and could be applied as a potential symbiotic strategy to assist in the alleviation of UC.