MUC1 Expression Research Articles

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.

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.

Emodin Inhibited MUC5AC Mucin Gene Expression via Affecting EGFR-MAPK-Sp1 Signaling Pathway in Human Airway Epithelial Cells.

The aim of this study was to evaluate emodin, a natural trihydroxyanthraquinone compound found in the roots and barks of several plants including rhubarb and buckthorn, might attenuate epidermal growth factor (EGF)-induced airway MUC5AC mucin gene expression. The human pulmonary mucoepidermoid NCI-H292 cells were pretreated with for 30 min and then stimulated with EGF for the following 24 h. The effect of emodin on EGF-induced mitogen-activated protein kinase (MAPK) signaling pathway was examined. As a result, emodin blocked the expression of MUC5AC mucin mRNA and production of mucous glycoprotein via suppressing the phosphorylation of EGF receptor (EGFR), phosphorylation of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) 1 and 2 (MEK1/2), phosphorylation of p38 MAPK, phosphorylation of ERK 1/2 (p44/42), and the nuclear expression of specificity protein-1 (Sp1). These findings imply that emodin has a potential to mitigate EGF-stimulated mucin gene expression by inhibiting the EGFR-MAPK-Sp1 signaling pathway, in NCI-H292 cells.

Solid-State Fermentation of Wheat Bran with Clostridium butyricum: Impact on Microstructure, Nutrient Release, Antioxidant Capacity, and Alleviation of Ulcerative Colitis in Mice.

This study investigated the effects of solid-state fermentation with Clostridium butyricum on the microstructure of wheat bran, the release of dietary fiber and phenolic compounds, and antioxidant capacity. Compared with unfermented wheat bran, insoluble dietary fiber and phytic acid content decreased, whereas soluble dietary fiber and water-extractable arabinoxylan content increased in C. butyricum culture. Because of the increased release of phenolic compounds, such as ferulic acid and apigenin, and organic acids, such as isobutyric acid, the antioxidant capacity of the culture was considerably improved. Furthermore, the culture of C. butyricum treated with dextran sulfate sodium-induced ulcerative colitis in mice enhanced the expression of intestinal mucus and tight-junction proteins, modulating the gut microbiota structure, increasing the levels of short-chain fatty acids in the intestine, and restoring the essential functions of the gut microbiota. These anti-inflammatory effects stemmed from the combined action of various effective components.

Jianpi-Huatan-Huoxue-Anshen formula ameliorates gastrointestinal inflammation and microecological imbalance in chemotherapy-treated mice transplanted with H22 hepatocellular carcinoma.

Jianpi-Huatan-Huoxue-Anshen formula [Tzu-Chi cancer-antagonizing & life-protecting II decoction (TCCL)] is a Chinese medical formula that has been clinically shown to reduce the gastrointestinal side effects of chemotherapy in cancer patients and improve their quality of life. However, its effect and mechanism on the intestinal microecology after chemotherapy are not yet clear. To discover the potential mechanisms of TCCL on gastrointestinal inflammation and microecological imbalance in chemotherapy-treated mice transplanted with hepatocellular carcinoma (HCC). Ninety-six mice were inoculated subcutaneously with HCC cells. One week later, the mice received a large dose of 5-fluorouracil by intraperitoneal injection to establish a HCC chemotherapy model. Thirty-six mice were randomly selected before administration, and feces, ileal tissue, and ileal contents were collected from each mouse. The remaining mice were randomized into normal saline, continuous chemotherapy, Yangzheng Xiaoji capsules-treated, and three TCCL-treated groups. After treatment, feces, tumors, liver, spleen, thymus, stomach, jejunum, ileum, and colon tissues, and ileal contents were collected. Morphological changes, serum levels of IL-1β, IL-6, IL-8, IL-10, IL-22, TNF-α, and TGF-β, intestinal SIgA, and protein and mRNA expression of ZO-1, NF-κB, Occludin, MUC-2, Claudin-1, and IκB-α in colon tissues were documented. The effect of TCCL on the abundance and diversity of intestinal flora was analyzed using 16S rDNA sequencing. TCCL treatment improved thymus and spleen weight, thymus and spleen indexes, and body weight, decreased tumor volumes and tumor tissue cell density, and alleviated injury to gastric, ileal, and colonic mucosal tissues. Among proteins and genes associated with inflammation, IL-10, TGF-β, SIgA, ZO-1, MUC-2, and Occludin were upregulated, whereas NF-κB, IL-1β, IL-6, TNF-α, IL-22, IL-8, and IκB-α were downregulated. Additionally, TCCL increased the proportions of fecal Actinobacteria, AF12, Adlercreutzia, Clostridium, Coriobacteriaceae, and Paraprevotella in the intermediate stage of treatment, decreased the proportions of Mucipirillum, Odoribacter, RF32, YS2, and Rikenellaceae but increased the proportions of p_Deferribacteres and Lactobacillus at the end of treatment. Studies on ileal mucosal microbiota showed similar findings. Moreover, TCCL improved community richness, evenness, and the diversity of fecal and ileal mucosal flora. TCCL relieves pathological changes in tumor tissue and chemotherapy-induced gastrointestinal injury, potentially by reducing the release of pro-inflammatory factors to repair the gastrointestinal mucosa, enhancing intestinal barrier function, and maintaining gastrointestinal microecological balance. Hence, TCCL is a very effective adjuvant to chemotherapy.

Gastric and Gastrointestinal-like Immunophenotypes In Conventional Endometrial Endometrioid Adenocarcinomas Including Endometrioid Adenocarcinomas with Mucinous Differentiation: Frequency and Diagnostic Implications

Abstract Introduction/Objective Mucinous carcinomas of the gastric/gastrointestinal type (MCG) are now recognized as a rare, clinically aggressive subtype of endometrial cancer [EMCa]. However, neither their full morphologic spectrum, nor their defining immunophenotype, has been clearly defined. Previous proposals for their recognition include at least focal immunohistochemical expression of gastrointestinal markers, minimality or absence of ER and possibly PAX8 expression, and the absence of an endometrioid carcinoma component. Herein, we assess the frequency of gastric and gastrointestinal immunophenotypes in conventional endometrioid carcinomas without any discernible gastric/gastrointestinal-type morphology. Methods/Case Report Immunohistochemical analyses for CK7, CK20, CDX2, ER, SATB2, MUC6, PAX8 were performed on 81 EMCa, comprised of consecutively archived cases of low grade endometrioid carcinoma (n=47), FIGO grade III endometrioid carcinoma (n=12), and endometrioid carcinomas with mucinous differentiation (n=22). None showed goblet cells or gastric-type morphology. Expression levels were quantified as H-scores on a standardized 0-300 scale. Results (if a Case Study enter NA) Significant subsets of all 3 groups showed expression of MUC6, CDX2, SATB2 and CK20, without any significant differences between the groups. 56%, 62%, 23% and 25% of cases expressed MUC6, CDX2, CK20 and SATB2 respectively. 37% co-expressed MUC6 and CDX2, 12% co-expressed CDX2 and CK20, 6% co-expressed MUC6, CDX2 and CK20 and 2.5% co-expressed CDX2, CK20 and SATB2. The expression levels were generally low across all groups, with average H scores for positive cases being 49.5 [range 1-250] for MUC6, 33.7 [range 1-285] for CDX2, 24.0 [range 1-270] for CK20, and 30.5 [range; 2-220] for SATB2. There was no statistically significant correlation between the expression of any of the 4 markers (CK20, CDX2, SATB2 or MUC6) and low ER or PAX8 expression. However, the only 2 cases with high CDX2 expression (H: >/=200) were also associated with low ER (H<50) expression, and one of these concurrently showed high CK20 (H: 270) and low PAX8 (H: 2) expression, suggestive of true intestinal differentiation. Conclusion MUC6, SATB2, CDX2, and CK20 are not uncommonly expressed at low levels in endometrioid carcinoma. As such, the expression of these markers cannot be the sole basis for defining the clinically aggressive EMCa with true gastric/gastrointestinal differentiation, and for distinguishing them from conventional endometrioid carcinomas.

Retracted] LOC102724163 promotes breast cancer cell proliferation and invasion by stimulating MUC19 expression

Retracted] LOC102724163 promotes breast cancer cell proliferation and invasion by stimulating MUC19 expression

Goblet cell differentiation subgroups in colorectal cancer

The poor prognosis of relatively undifferentiated cancers has long been recognized, suggesting that selection against differentiation and in favor of uncontrolled growth is one of the most powerful drivers of cancer progression. Goblet cells provide the mucous surface of the gut, and when present in colorectal cancers (CRC), the cancers are called mucinous. We have used the presence of MUC2, the main mucous product of goblet cells, and an associated gene product, TFF3, to classify a large panel of nearly 80 CRC-derived cell lines into five categories based on their levels of MUC2 and TFF3 expression. We have then shown that these five patterns of expression can be easily identified in the direct analysis of tumor specimens allowing a much finer characterization of CRCs with respect to the presence of goblet cell differentiation. In particular, about 30% of all CRCs fall into the category of expressing TFF3 but not MUC2, which has not previously been acknowledged. Using the cell line data, we suggest that there are up to 12 genes (MUC2, TFF3, ATOH1, SPDEF, CDX1, CDX2, GATA6, HES1, ETS2, OLFM4, TOX3, and LGR5) that may be involved in selection against goblet cell differentiation in CRC by changes in methylation rather than mutations. Of these, LGR5, which is particularly associated with lack of goblet cell features, may function in the control of differentiation rather than direct control of cell growth, as has so far mostly been assumed. These results emphasize the importance of methylation changes in driving cancer progression.

Salivary Transmembrane Mucins of the MUC1 Family (CA 15-3, CA 27.29, MCA) in Breast Cancer: The Effect of Human Epidermal Growth Factor Receptor 2 (HER2)

The MUC1 family of transmembrane glycoproteins (CA 15-3, CA 27.29, MCA) is aberrantly expressed among patients with breast cancer. Objectives: to measure the level of degradation products of MUC1, including CA 15-3, CA 27.29, and MCA, in the saliva of breast cancer patients and to describe the biochemical processes that influence their expression and the regulation of their biological functions. Methods: The case–control study included three groups (breast cancer, fibroadenomas, and healthy controls). All study participants provided saliva samples strictly before starting treatment. The levels of MUC1, including CA 15-3, CA 27.29, and MCA, free progesterone and estradiol, cytokines (MCP-1, VEGF, TNF-α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-18), and amino acids (Asp, Gln, Gly, His, Leu + Ile, Orn, Phe, Pro, Tyr) were determined. Results: It was shown that the levels of the MUC1 family in the saliva of patients with HER2-positive breast cancer were significantly lower compared to the control group. The level of pro-inflammatory cytokines and the level of free estradiol affected the expression of MUC1. We obtained a reliable relationship between the aggressive nature of tumor growth, an increased level of pro-inflammatory cytokines, a low level of free estradiol, and the suppressed expression of salivary MUC1. Conclusions: Among patients with aggressive breast cancer, a high level of pro-inflammatory cytokines, and a low level of free estradiol, there was an inhibition of the expression of pathologically unchanged glycoprotein MUC1 in saliva.

Interferon regulatory factor 7 alleviates the experimental colitis through enhancing IL-28A-mediated intestinal epithelial integrity

BackgroundThe incidence of inflammatory bowel disease (IBD) is on the rise in developing countries, and investigating the underlying mechanisms of IBD is essential for the development of targeted therapeutic interventions. Interferon regulatory factor 7 (IRF7) is known to exert pro-inflammatory effects in various autoimmune diseases, yet its precise role in the development of colitis remains unclear.MethodsWe analyzed the clinical significance of IRF7 in ulcerative colitis (UC) by searching RNA-Seq databases and collecting tissue samples from clinical UC patients. And, we performed dextran sodium sulfate (DSS)-induced colitis modeling using WT and Irf7−/− mice to explore the mechanism of IRF7 action on colitis.ResultsIn this study, we found that IRF7 expression is significantly reduced in patients with UC, and also demonstrated that Irf7−/− mice display heightened susceptibility to DSS-induced colitis, accompanied by elevated levels of colonic and serum pro-inflammatory cytokines, suggesting that IRF7 is able to inhibit colitis. This increased susceptibility is linked to compromised intestinal barrier integrity and impaired expression of key molecules, including Muc2, E-cadherin, β-catenin, Occludin, and Interleukin-28A (IL-28A), a member of type III interferon (IFN-III), but independent of the deficiency of classic type I interferon (IFN-I) and type II interferon (IFN-II). The stimulation of intestinal epithelial cells by recombinant IL-28A augments the expression of Muc2, E-cadherin, β-catenin, and Occludin. The recombinant IL-28A protein in mice counteracts the heightened susceptibility of Irf7−/− mice to colitis induced by DSS, while also elevating the expression of Muc2, E-cadherin, β-catenin, and Occludin, thereby promoting the integrity of the intestinal barrier.ConclusionThese findings underscore the pivotal role of IRF7 in preserving intestinal homeostasis and forestalling the onset of colitis.

Effect of Endurance Exercise Training on Gut Microbiota and ER Stress

Regular exercise as part of one’s lifestyle is well-recognized for its beneficial effect on several diseases such as cardiovascular disease and obesity; however, many questions remain unanswered regarding the effects of exercise on the gut environment. This study aimed to investigate the impact of long-term endurance exercise on modulating inflammation and endoplasmic reticulum (ER) stress. Fifteen-week-old male Sprague-Dawley (SD) rats were subjected to six months of endurance treadmill training, while age-matched controls remained sedentary. Results showed that IL-6 mRNA levels in colon tissues were significantly higher in the exercise group compared to the sedentary group. Exercise activated a significant ER stress-induced survival pathway by increasing BiP and phosphorylation of eIF2α (p-eIF2α) expressions in the liver and colon, while decreasing CHOP in the liver. Gene expressions of MUC2, Occludin, and Claudin-2 were increased in the colon of the exercise group, indicating enhanced intestinal integrity. Furthermore, the data showed a positive correlation between microbiota α-diversity and BiP (r = 0.464~0.677, p < 0.05). Populations of Desulfovibrio C21 c20 were significantly greater in the exercise group than the sedentary group. Additionally, predicted functions of the gut microbial community in terms of enzymes and pathways supported the enhancement of fatty-acid-related processes by exercise. These findings suggest that prolonged endurance exercise can affect the colon environment, which is likely related to changes in inflammation, ER stress, mucin layers and tight junctions, associated with modifications in the gut microbiome.

Deficiency of SLC26A3 promotes jejunal barrier damage in metabolic disease-susceptible transgenic pigs

Intestinal disorders are common in metabolic syndrome. However, their pathogenesis is still not fully understood. Pig and human intestines are highly similar in terms of associated metabolic processes. Here, we successfully constructed a metabolic disease-susceptible transgenic (TG) Bama pig model by knocking in three humanized disease risk genes with the CRISPR/Cas9 technique to assess its potential as a model for human intestinal diseases and explore the possible pathological mechanisms involved. We found that jejunal barrier integrity was disrupted and that the infiltration of inflammatory cells increased in TG pigs after high-fat and high-sucrose diet (HFHSD) treatment. We revealed significant differences in the transcriptome, associated microbiome profiles and microbial metabolite short-chain fatty acid (SCFA) content of the jejunum of TG pigs. Notably, we found that SLC26A3 was significantly downregulated in TG pigs. Knockdown or overexpression of the SLC26A3 gene in IPEC-J2 cells significantly affected the expression of MUC2, MUC13 and occludin. Furthermore, in vitro experiments further verified that CDX2 directly regulated the expression of SLC26A3. Mechanistically, CDX2 mediated intestinal barrier function by enhancing the expression of SLC26A3 by binding to its promoter region between −1120 and − 1070 bp. TG pigs represent a promising model that provides new insights into preclinical research on human intestinal metabolic diseases associated with metabolic disorders and revealed that SLC26A3 may be a potential therapeutic target for intestinal metabolic diseases.

Protective Effect of IgY Embedded in W/O/W Emulsion on LPS Enteritis-Induced Colonic Injury in Mice.

Chicken yolk immunoglobulin (IgY), an immunologically active component, is used as an alternative to antibiotics for the treatment of enteritis. In this study, IgY was embedded in a W/O/W emulsion to overcome the digestive barrier and to investigate the protective effect of IgY against LPS-induced enteritis in mice. Four different hydrophilic emulsifiers (T80, PC, SC, and WPI) were selected to prepare separate W/O/W emulsions for encapsulating IgY. The results showed that the IgY-embedded double emulsion in the WPI group was the most effective. IgY embedded in the W/O/W emulsion could reduce the damage of LPS to the mouse intestine and prevent LPS-induced intestinal mucosal damage in mice. It increased the number of cup cells, promoted the expression of Muc2, and increased the mRNA expression levels of KLF3, TFF3, Itln1, and Ang4 (p < 0.05). It also enhanced the antioxidant capacity of the colon tissue, reduced the level of inflammatory factors in the colon tissue, and protected the integrity of the colon tissue. Stable embedding of IgY could be achieved using the W/O/W emulsion. In addition, the IgY-embedded W/O/W emulsion can be used as a dietary supplement to protect against LPS-induced enteritis in mice.

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.

Terminal deoxynucleotidyl transferase (TdT) based template-free signal amplification for the detection of exosomes in MUC1-positive cells

The Mucin1 (MUC1) protein, involved in cytoprotective and signaling pathways, is abnormally elevated in various cancers, making it a key cancer indicator. Exosomes, which reflect the status of their originating cells, offer potential for cancer diagnosis. Thus, developing a method to detect MUC1-positive exosomes is crucial for the early diagnosis of certain cancers. In this study, we developed a highly sensitive, specific, and simple UV–visible signal amplification method to detect MUC1-positive exosomes using terminal deoxynucleotidyl transferase (TdT). Initially, exosomes were captured on magnetic beads using a CD63 aptamer(apt). The Primer-AuNPs-MUC1 apt complex which we synthesized by low pH loading method was then attached MUC1 proteins on the surface of the exosomes to create a sandwich structure. TdT catalyzed the extension of Biotin-dATP at the 3′ end of the primer, introducing multiple biotin sites into the sandwich structure. These sites subsequently bound multiple streptavidin-horseradish peroxidase (streptavidin-HRP), which catalyzed the oxidative color change of the substrate, which can be detected by colorimetric method. This method can detect A549 exosomes in the range of 1.4E+6 to 4.2E+8 particles/mL and shows high specificity for cell lines with different MUC1 expression. Additionally, it successfully distinguished cholangiocarcinoma (CCA) patients (n=11) from healthy individuals (n=7) in clinical serum assays, demonstrating good performance in real sample detection.

TGF-β2, EGF and FGF21 influence the suckling rat intestinal maturation

Some of the growth factors present in breast milk, such as transforming growth factor-β (TGF-β), epidermal growth factor (EGF) and fibroblast growth factor 21 (FGF21), play important roles in the development of the intestinal tract. The aim of this study was to determine the effect of a supplementation with TGF-β2, EGF and FGF21 on suckling rats intestinal maturation. For this purpose, Wistar rats were supplemented daily with TGF-β2, EGF or FGF21 throughout the suckling period. We evaluated the functionality of the intestinal epithelial barrier through an in vivo dextran permeability assay, and by a histomorphometric and immunohistochemical study. In addition, the intestinal gene expression of tight junction-associated proteins, mucins, toll-like receptors, and maturation markers was analyzed. Moreover, the intraepithelial lymphocyte (IEL) phenotypical composition was established.. During the suckling period, the supplementation with TGF-β2, EGF and FGF21 showed important signs of intestinal maturation. These results suggest that these molecules, present in breast milk, play a modulatory role in the maturation of the intestinal barrier function and the IEL composition during the suckling period.

Hesperidin and Fecal Microbiota Transplantation Modulate the Composition of the Gut Microbiota and Reduce Obesity in High Fat Diet Mice.

Obesity, which is associated with gut microbiota dysbiosis, low-grade chronic inflammation and intestinal barrier dysfunction, can cause a variety of chronic metabolic diseases. Phytochemical flavonoids have a variety of biological activities, among which there may besafe and effective anti-obesity solutions. We tested a plant-derived flavonoid hesperidin and fecal microbiota transplantation (FMT) to alleviate diet-induced obesity. High-fat diet (HFD)-fed mice were treated with hesperidin (100 and 200 mg/kg BW) and FMT. Results indicated that hesperidin had the effects of reducing obesity as indicated by reduction of body weight, fat accumulation and blood lipids, reducing inflammation as indicated by reduction of pro-inflammation factors including TNFα, IL-6, IL-1βand iNOS, and improving gut integrity as indicated by increasing colon length, reducing plasma gut permeability indicators iFABP and LBP, increased mRNA expression of mucus protein Muc2, tight junction p Claudin 2, Occludin and ZO-1 in the HFD-fed mice. The anti-obesity effects of hesperidin treatment have a dose-dependent manner. In addition, 16S rRNA-based gut microbiota analysis revealed that hesperidin selectively promoted the growth of Lactobacillus salivarius, Staphylococcus sciuri and Desulfovibrio C21_c20 while inhibiting Bifidobacterium pseudolongum, Mucispirillum schaedleri, Helicobacter ganmani and Helicobacter hepaticus in the HFD-fed mice. Horizontal feces transfer from the normal diet (ND)-fed mice to the HFD-fed mice conferred anti-obesity effects and transmitted some of the HFD-modulated microbes. We concluded that hesperidin and FMT both affect the reduction of body weight and improve HFD-related disorders in the HFD-fed mice possibly through modulating the composition of the gut microbiota.

Cosmetic implant placement in the female breast yields an altered local and systemic immune response: evidence for breast cancer immunosurveillance.

Women with cosmetic implants have lower rates of future breast cancer than the general population. We hypothesized the implant foreign body response could induce a local protective anti-cancer immunosurveillance. We expanded on our previous finding which showed women with breast implants have elevated antibody responses to certain breast cancer proteins. Blood samples and breast tissue were collected from women undergoing first time breast augmentation (implant-naive, IN) and revision breast augmentation (implant-exposed, IE). Sera were collected and antibody levels to common breast cancer proteins were quantified by enzyme-linked immunosorbent assay (ELISA). RT-PCR was performed on breast tissue samples to quantify immune-related gene expression levels between IN and IE. Bulk RNA sequencing was performed to identify differentially expressed genes and altered signaling pathways in the breasts of IN versus IE. In total, 188 patients were recruited (117 IN, 71 IE). Data demonstrated that IE patients had higher levels of antibodies to MUC-1, ER, and mammaglobin A compared to IN patients. MUC-1 expression was found to be higher in IE compared to IN breast tissue. RNA-seq analysis demonstrated upregulated pathways in IE breast tissue for B cell activation and development, Th2 related genes, T cell activation, chemotactic factors, and responses to estrogen. This is the first study to demonstrate that peri-implant inflammation extends beyond the implant capsule to breast parenchyma. Women with breast implants have more activated B cells in the breast parenchyma and elevated antibody responses to breast cancer antigen.