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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 [ABSTRACT FROM AUTHOR]

Background and Aim Methods Results Conclusions The first step towards developing a screening strategy for Barrett's esophagus (BE) is the identification of individuals in the community. Currently available tools include endoscopy, less‐invasive non‐endoscopic devices, and non‐invasive risk stratification models. We evaluated the cost of potential strategies for identification of BE as a first step towards screening.Two hypothetical cohorts of the general population aged ≥ 50 years with BE prevalence rates of 1.9% and 6.8% were modeled. Four potential screening tools were evaluated: (i) risk stratification based on non‐weighted clinical factors according to US/European guidelines, (ii) weighted risk stratification using algorithmic models, (iii) less‐invasive devices such as Cytosponge + trefoil factor 3 (TFF3), and (iv) endoscopy. Using a decision‐analytic model, the cost per BE case identified and the cost‐effectiveness were compared for six potential BE screening strategies based on combinations of the four screening tools; (i) + (iv), (ii) + (iv), (iii) + (iv), (i) + (iii) + (iv), (ii) + (iii) + (iv), and only (iv).The cost per BE case identified was lowest for the weighted risk stratification followed by Cytosponge‐TFF3 then endoscopy strategy at both 1.9% and 6.8% BE prevalences (US$9282 and US$3406, respectively) although it was sensitive to the cost of less‐invasive devices. This strategy was also most cost‐effective for a BE prevalence of 1.9%. At BE prevalence of 6.8%, the Cytosponge‐TFF3 followed by endoscopy strategy was most cost‐effective.Incorporating weighted risk stratification and less‐invasive devices such as Cytosponge‐TFF3 into BE screening strategies has a potential to cost‐effectively identify BE in the community although device cost and the community prevalence of BE will impact the optimal strategy. [ABSTRACT FROM AUTHOR]

Background/Objectives: Trefoil factor 1 (TFF1) plays a role in the mucus barrier. Methods: To evaluate the prevalence of TFF1 expression in cancer, a tissue microarray containing 18,878 samples from 149 tumor types and 608 samples of 76 normal tissue types was analyzed through immunohistochemistry (IHC). Results: TFF1 staining was detectable in 65 of 149 tumor categories. The highest rates of TFF1 positivity were found in mucinous ovarian carcinomas (76.2%), colorectal adenomas and adenocarcinomas (47.1–75%), breast neoplasms (up to 72.9%), bilio-pancreatic adenocarcinomas (42.1–62.5%), gastro-esophageal adenocarcinomas (40.4–50.0%), neuroendocrine neoplasms (up to 45.5%), cervical adenocarcinomas (39.1%), and urothelial neoplasms (up to 24.3%). High TFF1 expression was related to a low grade of malignancy in non-invasive urothelial carcinomas of the bladder (p = 0.0225), low grade of malignancy (p = 0.0003), estrogen and progesterone receptor expression (p < 0.0001), non-triple negativity (p = 0.0005) in invasive breast cancer of no special type, and right-sided tumor location (p = 0.0021) in colorectal adenocarcinomas. Conclusions: TFF1 IHC has only limited utility for the discrimination of different tumor entities given its expression in many tumor entities. The link between TFF1 expression and parameters of malignancy argues for a relevant biological role of TFF1 in cancer. TFF1 may represent a suitable therapeutic target due to its expression in only a few normal cell types. [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD) may be inherited, as recently shown with the identification of single nucleotide polymorphisms (SNPs or "snips") on a 250 kb DNA fragment that encodes 92 proteins associated with CVD. CVD is also triggered by microbial dysbiosis, microbial metabolites, metabolic disorders, and inflammatory intestinal epithelial cells (IECs). The epithelial cellular adhesion molecule (Ep-CAM) and trefoil factor 3 (TFF3) peptide keeps the gut wall intact and healthy. Variations in Ep-CAM levels are directly linked to changes in the gut microbiome. Leptin, plasminogen activator inhibitor 1 (PAI1), and alpha-1 acid glycoprotein 1 (AGP1) are associated with obesity and may be used as biomarkers. Although contactin 1 (CNTN1) is also associated with obesity and adiposity, it regulates the bacterial metabolism of tryptophan (Trp) and thus appetite. A decrease in CNTN1 may serve as an early warning of CVD. Short-chain fatty acids (SCFAs) produced by gut microbiota inhibit pro-inflammatory cytokines and damage vascular integrity. Trimethylamine N-oxide (TMAO), produced by gut microbiota, activates inflammatory Nod-like receptors (NLRs) such as Nod-like receptor protein 3 (NLRP3), which increase platelet formation. Mutations in the elastin gene (ELN) cause supra valvular aortic stenosis (SVAS), defined as the thickening of the arterial wall. Many of the genes expressed by human cells are regulated by gut microbiota. The identification of new molecular markers is crucial for the prevention of CVD and the development of new therapeutic strategies. This review summarizes the causes of CVD and identifies possible CVD markers. [ABSTRACT FROM AUTHOR]

Bleomycin (BLM) induces lung injury, leading to inflammation and pulmonary fibrosis. Regulatory T cells (Tregs) maintain self-tolerance and control host immune responses. However, little is known about their involvement in the pathology of pulmonary fibrosis. Here we show that a unique Treg subset expressing trefoil factor family 1 (Tff1) emerges in the BLM-injured lung. These Tff1-expressing Tregs (Tff1-Tregs) were induced by IL-33. Moreover, although Tff1 ablation in Tregs did not change the pathological condition, selective ablation of Tff1-Tregs using an intersectional genetic method promoted pro-inflammatory features of macrophages in the injured lung and exacerbated the fibrosis. Taken together, our study revealed the presence of a unique Treg subset expressing Tff1 in BLM-injured lungs and their critical role in the injured lung to ameliorate fibrosis. [ABSTRACT FROM AUTHOR]

Background: Multiple studies have shown that tumor-associated macrophages (TAMs) promote cancer initiation and progression. However, the reprogramming of macrophages in the tumor microenvironment (TME) and the cross-talk between TAMs and malignant subclones in intrahepatic cholangiocarcinoma (iCCA) has not been fully characterized, especially in a spatially resolved manner. Deciphering the spatial architecture of variable tissue cellular components in iCCA could contribute to the positional context of gene expression containing information pathological changes and cellular variability. Methods: Here, we applied spatial transcriptomics (ST) and digital spatial profiler (DSP) technologies with tumor sections from patients with iCCA. Results: The results reveal that spatial inter- and intra-tumor heterogeneities feature iCCA malignancy, and tumor subclones are mainly driven by physical proximity. Tumor cells with TME components shaped the intra-sectional heterogenetic spatial architecture. Macrophages are the most infiltrated TME component in iCCA. The protein trefoil factor 3 (TFF3) secreted by the malignant subclone can induce macrophages to reprogram to a tumor-promoting state, which in turn contributes to an immune-suppressive environment and boosts tumor progression. Conclusions: In conclusion, our description of the iCCA ecosystem in a spatially resolved manner provides novel insights into the spatial features and the immune suppressive landscapes of TME for iCCA. [ABSTRACT FROM AUTHOR]

Background: Chronic atrophic gastritis (CAG) is an important precursor of gastric cancer(GC), and there is currently a lack of reliable non-invasive diagnostic markers. This study aims to find a biomarker for non-invasive screening of CAG in the community. Methods: A total of 540 individuals were enrolled (test set = 385, validation set = 155). ROC curve analysis was used to evaluate the diagnostic significance of serum Trefoil Factor 3 (TFF3) alone or in combination with pepsinogen (PG) for CAG in the test and validation set. Furthermore, the diagnostic value of TFF3 and PG in different Helicobacter pylori (H. pylori) infection states was studied. Results: When compared with chronic superficial gastritis (CSG), the expression level of serum TFF3 in the CAG was higher (27 ng/ml vs 19.61, P < 0.001). ROC curve analysis found that the sensitivity, specificity, and area under the curve (AUC) of CAG diagnosis using serum TFF3 alone at the optimal cut-off value of 26.55 ng/ml were 0.529, 0.87, and 0.739, respectively. When TFF3 was combined with The Ratio of PGI to PGII (PGR), the AUC and specificity reached 0.755 and 0.825, respectively. TFF3 individual or combined with PGR had good predictive value, especially in the H. Pylori negative patients. Conclusion: TFF3 combined with PGR can effectively predict CAG, especially in patients with H. pylori negative. [ABSTRACT FROM AUTHOR]

Background and Aims: Cholemic nephropathy is a cause of acute kidney injury occurring in patients with jaundice. The aim of this study was to evaluate early renal function impairment in patients with mild acute hyperbilirubinemia in the absence of alterations of the common parameters used in clinical practice (serum creatinine or urea) and with normal renal morphology. We studied urinary biomarkers of tubular damage urinary neutrophil gelatinase‐associated lipocalin (u‐NGAL), urinary beta‐2‐microglobulin (u‐B2M), urinary osteopontin (u‐OPN), urinary trefoil factor 3 (u‐TFF3) and urinary Cystatin C (u‐Cys). Methods: This is a case‐control study investigating the following urinary biomarkers of tubular damage: u‐NGAL, u‐B2M, u‐OPN, u‐TFF3 and u‐Cys, in patients with mild acute hyperbilirubinemia. Seventy‐four patients were included in this study: 36 patients with jaundice and 38 patients without jaundice. Results: Subjects with jaundice (total bilirubin 12.4 ± 7.3 mg/dL) showed higher u‐NGAL, u‐B2M, u‐OPN, u‐TFF3 and u‐Cys compared with controls. After logistic regression analyses, including the following independent variables: age, estimated Glomerular Filtration Rate (eGFR), haemoglobin, diabetes, hypertension and jaundice, we observed a higher risk of elevated u‐NGAL values (OR = 3.8, 95% CI 1.07–13.5, p =.03) and u‐B2M (OR = 9.4, 95% CI 2.3–38.9, p =.0018) in jaundiced subjects. Moreover, urinary biomarkers had a direct correlation with serum cholestasis indexes. Conclusions: This study demonstrated increased urinary biomarkers of tubular damage (u‐NGAL, u‐B2M, u‐OPN, u‐TFF3, and u‐Cys) in patients with mild hyperbilirubinemia in comparison with a control group. These findings suggest early renal tubular damage in the absence of alterations of the normal parameters used in clinical practice (eGFR, serum urea and renal morphology). [ABSTRACT FROM AUTHOR]

Exocrine-to-endocrine cross talk in the pancreas is crucial to maintain β-cell function. However, the molecular mechanisms underlying this cross talk are largely undefined. Trefoil factor 2 (Tff2) is a secreted factor known to promote the proliferation of β-cells in vitro, but its physiological role in vivo in the pancreas is unknown. Also, it remains unclear which pancreatic cell type expresses Tff2 protein. We therefore created a mouse model with a conditional knockout of Tff2 in the murine pancreas. We find that the Tff2 protein is preferentially expressed in acinar but not ductal or endocrine cells. Tff2 deficiency in the pancreas reduces β-cell mass on embryonic day 16.5. However, homozygous mutant mice are born without a reduction of β-cells and with acinar Tff3 compensation by day 7. When mice are aged to 1 year, both male and female homozygous and male heterozygous mutants develop impaired glucose tolerance without affected insulin sensitivity. Perifusion analysis reveals that the second phase of glucose-stimulated insulin secretion from islets is reduced in aged homozygous mutant compared with controls. Collectively, these results demonstrate a previously unknown role of Tff2 as an exocrine acinar cell-derived protein required for maintaining functional endocrine β-cells in mice. Article Highlights: Exocrine-to-endocrine cross talk is important in maintaining pancreatic cell homeostasis, but the molecular mechanisms remain largely undefined. In the pancreas, the physiological role of the secreted factor Tff2 and the cell type that expresses Tff2 has been unclear. Pancreatic acinar cells are the major cell type expressing Tff2 protein, and specific loss of Tff2 in the pancreas reduces β-cells during development and attenuates glucose-stimulated insulin secretion during aging in conditional Tff2 knockout mice. Tff2 is a positive exocrine-produced factor required for the development and function of endocrine β-cells, which has implications in diabetes disease progression and therapy. [ABSTRACT FROM AUTHOR]

Objective: To investigate the diagnostic value of contrast-enhanced ultrasound combined with serum intestinal trefoil factor (ITF) in non-small cell lung cancer (NSCLC). Methods: From January 2021 to June 2023, 130 patients with pulmonary space-occupying lesions who underwent surgical treatment in our hospital were included as the study subjects. All patients underwent contrast-enhanced ultrasonography and serum ITF detection before operation. According to the postoperative pathological results, the patients were divided into NSCLC group (n=58) and benign lung tumor group (n=72). Contrast-enhanced ultrasound parameters and serum ITF levels were compared between the two groups. The receiver operating characteristic curve (ROC) was drawn to analyze the diagnostic value of contrast-enhanced ultrasound parameters, serum ITF and their combination for NSCLC. Results: RT, TP, AT2 and△AT in NSCLC group were higher than those in benign lung tumor group (P＜0. 05). The level of serum ITF in NSCLC group was higher than that in benign lung tumor group (P＜0. 05). The results of ROC curve analysis of contrast-enhanced ultrasound parameters showed that the largest area under the curve (AUC) was△AT, and when △AT ≥ 3. 14s, its specificity was 88. 29%, which had high diagnostic value for NSCLC. ROC curve analysis of serum ITF showed that AUC was 0. 735, and when serum ITF≥1073. 82 pg/mL, its specificity was81. 06%, which had certain diagnostic value for NSCLC. The ROC curve analysis of contrast-enhanced ultrasound parameters combined with serum ITF showed that the AUC was 0. 916 and the specificity was 91. 20 %, which had the best diagnostic value for NSCLC. Conclusion: Contrast-enhanced ultrasound combined with serum ITF has a high diagnostic value for NSCLC, which is helpful for the differential diagnosis of benign and malignant lung tumors, and provides a reliable reference for the clinical diagnosis and treatment of patients. [ABSTRACT FROM AUTHOR]

Obesity is associated with changes in the gut microbiota, as well as with increased permeability of the intestinal wall. In 130 non-obese volunteers, 57 patients with metabolically healthy obesity (MHO), and 76 patients with metabolically unhealthy obesity (MUHO), bacterial DNA was isolated from stool samples, and the 16S rRNA gene was sequenced. The metabolic profile of the microbiota predicted by PICRUSt2 (https://huttenhower.sph.harvard.edu/picrust/) was more altered in patients with MUHO than MHO. Obesity, especially MUHO, was accompanied by an increase in the ability of the gut microbiota to degrade energy substrates, produce energy through oxidative phosphorylation, synthesize water-soluble vitamins (B1, B6, B7), nucleotides, heme, aromatic amino acids, and protective structural components of cells. Such changes may be a consequence of the microbiota adaptation to the MUHO-specific conditions. Thus, a vicious circle is formed, when MUHO promotes the depletion of the gut microbiome, and further degeneration of the latter contributes to the pathogenesis of metabolic disorders. The concentration of the trefoil factor family (TFF) in the serum of the participants was also determined. In MHO and MUHO patients, the TFF2 and TFF3 levels were increased, but we did not find significant associations of these changes with the metabolic profile of the gut microbiota. [ABSTRACT FROM AUTHOR]

Background: Currently utilized serum tumor markers and fecal immunochemical tests do not have sufficient diagnostic power for colorectal cancer (CRC) due to their low sensitivities. To establish non-invasive urinary protein biomarkers for early CRC diagnosis, we performed stepwise analyses employing urine samples from CRCs and healthy controls (HCs). Methods: Among 474 urine samples, 363 age- and sex-matched participants (188 HCs, 175 stage 0–III CRCs) were randomly divided into discovery (16 HCs, 16 CRCs), training (110 HCs, 110 CRCs), and validation (62 HCs, 49 CRCs) cohorts. Results: Of the 23 urinary protein candidates comprehensively identified from mass spectrometry in the discovery cohort, urinary levels of dipeptidase 1 (uDPEP1) and Trefoil factor1 (uTFF1) were the two most significant diagnostic biomarkers for CRC in both training and validation cohorts using enzyme-linked immunosorbent assays. A urinary biomarker panel comprising uDPEP1 and uTFF1 significantly distinguished CRCs from HCs, showing area under the curves of 0.825–0.956 for stage 0–III CRC and 0.792–0.852 for stage 0/I CRC. uDPEP1 and uTFF1 also significantly distinguished colorectal adenoma (CRA) patients from HCs, with uDPEP1 and uTFF1 increasing significantly in the order of HCs, CRA patients, and CRC patients. Moreover, expression levels of DPEP1 and TFF1 were also significantly higher in the serum and tumor tissues of CRC, compared to HCs and normal tissues, respectively. Conclusions: This study established a promising and non-invasive urinary protein biomarker panel, which enables the early detection of CRC with high sensitivity. [ABSTRACT FROM AUTHOR]

Background and Aims: Pancreatic cancer is one of the most lethal malignancies, partly due to resistance to conventional chemotherapy. The chemoresistance of malignant tumors is associated with epithelial‐mesenchymal transition (EMT) and the stemness of cancer cells. The aim of this study is to investigate the availability and functional mechanisms of trefoil factor family 1 (TFF1), a tumor‐suppressive protein in pancreatic carcinogenesis, to treat pancreatic cancer. Methods: To investigate the role of endogenous TFF1 in human and mice, specimens of human pancreatic cancer and genetically engineered mouse model of pancreatic cancer (KPC/TFF1KO; Pdx1‐Cre/LSL‐KRASG12D/LSL‐p53R172H/TFF1−/−) were analyzed by immunohistochemistry (IHC). To explore the efficacy of extracellular administration of TFF1, recombinant and chemically synthesized TFF1 were administered to pancreatic cancer cell lines, a xenograft mouse model and a transgenic mouse model. Results: The deficiency of TFF1 was associated with increased EMT of cancer cells in mouse models of pancreatic cancer, KPC. The expression of TFF1 in cancer cells was associated with better survival rate of the patients who underwent chemotherapy, and loss of TFF1 deteriorated the benefit of gemcitabine in KPC mice. Extracellular administration of TFF1 inhibited gemcitabine‐induced EMT, Wnt pathway activation and cancer stemness, eventually increased apoptosis of pancreatic cancer cells in vitro. In vivo, combined treatment of gemcitabine and subcutaneous administration of TFF1 arrested tumor growth in xenograft mouse model and resulted in the better survival of KPC mice by inhibiting EMT and cancer stemness. Conclusion: These results indicate that TFF1 can contribute to establishing a novel strategy to treat pancreatic cancer patients by enhancing chemosensitivity. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "Urinary dipeptidase 1 and trefoil factor 1 are promising biomarkers for early diagnosis of colorectal cancer" published in the Journal of Gastroenterology. The correction states that there was an error in Table 2 of the article, where the data were mistakenly listed under the wrong columns. The correct Table 2 is provided in the correction. The article discusses the urinary protein levels normalized to urinary creatinine levels as potential biomarkers for early diagnosis of colorectal cancer. The document also includes a table of data related to the levels of various substances in the urine of healthy individuals and those with colorectal cancer. The data is presented in terms of the mean and interquartile range for each substance. The document also includes a note from the publisher regarding a correction to the supplementary file. [Extracted from the article]

Background: Angiogenesis is a critical step in colorectal cancer growth, progression and metastasization. CT are routine imaging examinations for preoperative clinical evaluation in colorectal cancer patients. This study aimed to investigate the predictive value of preoperative CT enhancement rate (CER) and CT perfusion parameters on angiogenesis in colorectal cancer, as well as the association of preoperative CER and CT perfusion parameters with serum markers. Methods: This retrospective analysis included 42 patients with colorectal adenocarcinoma. Median of microvessel density (MVD) as the cut-off value, it divided 42 patients into high-density group (MVD ≥ 35/field, n = 24) and low-density group (MVD < 35/field, n = 18), and 25 patients with benign colorectal lesions were collected as the control group. Statistical analysis of CER, CT perfusion parameters, serum markers were performed in all groups. Receiver operating curves (ROC) were plotted to evaluate the diagnostic efficacy of relevant CT perfusion parameters for tumor angiogenesis; Pearson correlation analysis explored potential association between CER, CT perfusion parameters and serum markers. Results: CER, blood volume (BV), blood flow (BF), permeability surface (PS) and carbohydrate antigen 19 − 9 (CA19-9), carbohydrate antigen 125 (CA125), carcinoembryonic antigen (CEA), trefoil factor 3 (TFF3), vascular endothelial growth factor (VEGF) in colorectal adenocarcinoma were significantly higher than those in the control group, the parameters in high-density group were significantly higher than those in the low-density group (P < 0.05); however, the time to peak (TTP) of patients in colorectal adenocarcinoma were significantly lower than those in the control group, and the high-density group showed a significantly lower level compared to the low-density group (P < 0.05). The combined parameters BF + TTP + PS and BV + BF + TTP + PS demonstrated the highest area under the curve (AUC), both at 0.991. Pearson correlation analysis showed that the serum levels of CA19-9, CA125, CEA, TFF3, and VEGF in patients showed positive correlations with CER, BV, BF, and PS (P < 0.05), while these indicators exhibited negative correlations with TTP (P < 0.05). Conclusions: Some single and joint preoperative CT perfusion parameters can accurately predict tumor angiogenesis in colorectal adenocarcinoma. Preoperative CER and CT perfusion parameters have certain association with serum markers. [ABSTRACT FROM AUTHOR]

Objective: Despite the advances in treatment, breast cancer (BC) remains a major cause of death in women. This study aims to evaluate the prognostic significance of detecting circulating tumor cells (CTCs) and disseminated tumor cells (DTCs) in paired peripheral blood (PB) and bone marrow (BM) samples obtained both before and after adjuvant chemotherapy from patients with operable BC. Materials and Methods: In this experimental study, from 160 patients with primary BC, we collected 160 PB and BM samples before and we could be able to collect PB and BM samples from 100 of them after adjuvant chemotherapy. The expression level of cytokeratin 19 (CK19), carcinoembryonic antigen (CEA), mammaglobin 1 (MGB1), mucin 2 (MUC2) and trefoil factor 1 (TFF1) mRNAs in the PB/BM samples were analyzed by quantitative real-time polymerase chain reaction (PCR). Results: Multivariate Cox regression analyses indicated that the detection of CK19 mRNA-positive CTCs/DTCs either before or after adjuvant chemotherapy was an independent factor for prognosis associated with decreased disease-free survival (DFS). Patients with tumor cells detected in both PB and BM and patients with persistent detection of tumor cells before and after chemotherapy had worse outcomes compared to those with tumor cells detected in one or neither of the compartments. Conclusion: This study suggests that the detection of CK19 mRNA-positive CTCs/DTCs either before or after adjuvant chemotherapy could be an independent predictor of DFS in operable BC patients. [ABSTRACT FROM AUTHOR]

Background: Trefoil factor 3 (TFF-3) is a peptide that restores the epithelium as protection against injury. Recently, TFF-3 was shown to be expressed in kidney tubular cells and was associated with fbrosis. We aimed to determine whether TFF-3 is associated with kidney outcomes. Methods: We evaluated TFF-3 expression and its relationship with mesangial hypercellularity, endocapillary hypercellularity, segmental glomerulosclerosis, tubular atrophy/interstitial fbrosis and crescents (MEST-C) score, tumor necrosis factor alpha (TNF-α), interleukin-10 (IL-10), and transforming growth factor-beta (TGF-β) expression in the kidney. We included 28 immunoglobulin A (IgA) patients with initial estimated glomerular fltration rate (eGFR) ≥ 30 mL/min/1.73m2 and proteinuria ≥0.5 g/day. Kidney biopsies were scored using MEST-C and were stained for TFF-3, IL10, TGF-β, and TNF-α. Results: Mean patient age was 37.0 ± 13.8 years and eGFR was 74.6 ± 41.2 mL/min/1.73 m2 . Patients were followed for 9.1 ± 3.6 years. Trefoil factor 3 was positive in 67.9% of patients exclusively in tubular cells. Tumor growth factor-β was also observed only in tubular cells in 71.4% of patients and was higher in TFF-3-positive patients (89.5% vs. 22.2%, P < .05). When patients with and without TFF-3 staining were compared, there was no diference in age, eGFR, albumin, or proteinuria. Yearly eGFR change was also similar (−0.5 ± 2.3 vs. −1.3 ± 2.4 mL/min/1.73 m2, P = .44). Trefoil factor 3 was not associated with kidney survival. The MEST-C score was not correlated with TFF-3. Trefoil factor 3 staining showed correlation with TGF-β but was not associated with kidney survival in IgA patients. Conclusion: Findings of the study imply TFF-3 is not a marker of permanent damage but might simply be a marker of the repair of ongoing tubular injury. [ABSTRACT FROM AUTHOR]

TFF3 is a typical secretory poplypeptide of mucous epithelia belonging to the trefoil factor family (TFF) of lectins. In the intestine, respiratory tract, and saliva, TFF3 mainly exists as a high-molecular-mass complex with IgG Fc binding protein (FCGBP), which is indicative of a role in mucosal innate immunity. For the first time, we identified different forms of TFF3 in the endocervix, i.e., monomeric and homodimeric TFF3, as well as a high-molecular-mass TFF3-FCGBP complex; the latter also exists in a hardly soluble form. Immunohistochemistry co-localized TFF3 and FCGBP. Expression analyses of endocervical and post-menopausal vaginal specimens revealed a lack of mucin and TFF3 transcripts in the vaginal specimens. In contrast, genes encoding other typical components of the innate immune defense were expressed in both the endocervix and vagina. Of note, FCGBP is possibly fucosylated. Endocervical specimens from transgender individuals after hormonal therapy showed diminished expression, particularly of FCGBP. Furthermore, mucus swabs from the endocervix and vagina were analyzed concerning TFF3, FCGBP, and lysozyme. It was the aim of this study to illuminate several aspects of the cervico-vaginal innate immune barrier, which is clinically relevant as bacterial and viral infections are also linked to infertility, pre-term birth and cervical cancer. [ABSTRACT FROM AUTHOR]

Aims: This study aims to provide insight into sex‐specific cardiovascular protein profiles and their associations with adverse outcomes, which may contribute to a better understanding of heart failure (HF) pathophysiology and the optimal use of circulating proteins for prognostication in women and men. Methods and results: In 250 stable patients with HF with reduced ejection fraction (HFrEF), we performed trimonthly blood sampling (median follow‐up: 26 [17–30] months). We selected all baseline samples and two samples closest to the primary endpoint (PEP; composite of cardiovascular death, heart transplantation, left ventricular assist device implantation, and HF hospitalization) or one sample closest to censoring and applied the Olink Cardiovascular III panel. We used linear regression to study sex‐based differences in baseline levels and joint models to study differences in the prognostic value of serially measured proteins. In 66 women and 184 men (mean age of 66 and 67 years, respectively), 21% and 28% reached the PEP, respectively. Mean baseline levels of fatty acid‐binding protein 4, secretoglobin family 3A member 2, paraoxonase 3, and trefoil factor 3 were higher in women (Pinteraction: 0.001, 0.007, 0.018, and 0.049, respectively), while matrix metalloproteinase‐3, interleukin 1 receptor‐like 1, and myoglobin were higher in men (Pinteraction: <0.001, 0.001, and 0.049, respectively), independent of clinical characteristics. No significant differences between sexes were observed in the longitudinal associations of proteins with the PEP. Only peptidoglycan recognition protein 1 showed a suggestive interaction with sex for the primary outcome (Pinteraction = 0.028), without multiple testing correction, and was more strongly associated with adverse outcome in women {hazard ratio [HR] 3.03 [95% confidence interval (CI), 1.42 to 6.68], P = 0.008} compared with men [HR 1.18 (95% CI, 0.84 to 1.66), P = 0.347]. Conclusions: Although multiple cardiovascular‐related proteins show sex differences at baseline, temporal associations with the adverse outcome do not differ between women and men with HFrEF. [ABSTRACT FROM AUTHOR]

Pyloric gland adenoma (PGA) is a duodenal neoplasm expressing MUC6 and is often associated with high-grade dysplasia and adenocarcinoma. MUC6 secreted from the pyloric gland cells carries unique O-glycans exhibiting terminal α1,4-linked N-acetylglucosamine residues (αGlcNAc). The small peptide trefoil factor 2 (TFF2) is also secreted from pyloric gland cells and binds to αGlcNAc. We recently demonstrated that αGlcNAc serves as a tumor suppressor for gastric neoplasm including PGA, but the significance of TFF2 expression remains unknown. We examined 20 lesions representing low- and high-grade PGA in 22 cases by immunohistochemistry for αGlcNAc, TFF2, MUC6, MUC5AC, MUC2 and p53. αGlcNAc, TFF2 and MUC6 were co-expressed on the cell surface and a dot-like pattern in the cytosol in low-grade PGA lesions. High-grade PGA also expressed MUC6, but reduced αGlcNAc and TFF2 expression. The ratios of αGlcNAc or TFF2 to MUC6 score in high-grade PGA were significantly lower than low-grade PGA (P < 0.001). Co-expression of αGlcNAc-glycosylated MUC6 and TFF2 in PGA suggests the existence of αGlcNAc/TFF2 form complex in PGA cells, a finding consistent with our observations in non-neoplastic Brunner's gland cells. The decreased αGlcNAc and TFF2 expression are associated with high grade atypical cells, indicative of the malignant potential of PGA. [ABSTRACT FROM AUTHOR]

Objective: To investigate the relationship between preoperative trefoil factor 3 (TFF3）, heat shock protein 40 (HSP40）,neutrophil/lymphocyte ratio (NLR) and recurrence after tumor cell reduction surgery (CRS) in patients with epithelial ovarian cancer (EOC）. Methods: 140 EOC patients who received CRS treatment in Department of Gynecology of Nanjing Second Hospital from January2016 to May 2017 were selected, and they were divided into recurrent group and non recurrent group based on whether they recurred after CRS. Serum TFF3, HSP40, and NLR were detected and calculated. Single factor and multivariate logistic regression were used to analyze the influencing factors of recurrence after CRS in EOC patients, and the predictive value of recurrence after CRS in EOC patients were analyzed by Subjects’ Job Characteristics (ROC) Curve. Results: Following up for 5 years, 2 cases were lost and 138 EOC patients had a recurrence rate of 52.90% (73/138) after CRS. Compared with the non recurrence group, the recurrence group had a higher proportion of International Federation of Obstetrics and Gynecology (FIGO) stage IV, chemotherapy courses ≥6, and postoperative residual lesions with a maximum residual tumor diameter of ≤1 cm (R1）. The preoperative serum carbohydrate antigen (CA) 125, TFF3,HSP40, and NLR were increased (P＜0.05）. Multivariate logistic regression analysis showed that tumor diameter ≥3 cm, low differentiation, FIGO stage IV, residual lesions of R1 and TFF3 after surgery, HSP40, and increased NLR were independent risk factors for recurrence after CRS in EOC patients (P＜0.05）. ROC curve analysis showed that the area under the curve (AUC) of preoperative serum TFF3, HSP40, and NLR alone and in combination predicted recurrence after CRS in EOC patients were 0.766, 0.763, 0.765, and0.911, respectively. The AUC of preoperative serum TFF3, HSP40, and NLR combined predicted recurrence after CRS in EOC patients was the highest. Conclusion: Elevated levels of preoperative serum TFF3, HSP40, and NLR are independently associated with postoperative recurrence in EOC patients with CRS, and may serve as auxiliary predictive indicators for postoperative recurrence in EOC patients. The combined use of these three indicators has higher predictive value. [ABSTRACT FROM AUTHOR]

Trefoil factor family protein 3 (Tff3) protects the gastrointestinal mucosa and has a complex mode of action in different tissues. Here, we aimed to determine the effect of Tff3 deficiency on intestinal tissues in a long-term high-fat-diet (HFD)-fed model. A novel congenic strain without additional metabolically relevant mutations (Tff3-/-/C57Bl6NCrl strain, male and female) was used. Wild type (Wt) and Tff3-deficient mice of both sexes were fed a HFD for 36 weeks. Long-term feeding of a HFD induces different effects on the intestinal structure of Tff3-deficient male and female mice. For the first time, we found sex-specific differences in duodenal morphology. HFD feeding reduced microvilli height in Tff3-deficient females compared to that in Wt females, suggesting a possible effect on microvillar actin filament dynamics. These changes could not be attributed to genes involved in ER and oxidative stress, apoptosis, or inflammation. Tff3-deficient males exhibited a reduced cecal crypt depth compared to that of Wt males, but this was not the case in females. Microbiome-related short-chain fatty acid content was not affected by Tff3 deficiency in HFD-fed male or female mice. Sex-related differences due to Tff3 deficiency imply the need to consider both sexes in future studies on the role of Tff in intestinal function. [ABSTRACT FROM AUTHOR]

Simple Summary: Effective management of retinoblastoma (RB), a common childhood eye cancer, requires accurate diagnosis and monitoring during therapy. In this study, the liquid biopsy marker potential of the secreted trefoil family factor peptide 1 (TFF1), described as a biomarker of a more advanced RB subtype, was explored. TFF1 expression levels were investigated in aqueous humor (AH) of RB patients after enucleation and in RB patients undergoing intravitreal chemotherapy, and compared with TFF1 expression levels in RB patients' blood serum. AH showed consistent TFF1 levels in a subgroup of RB patients, remarkably decreasing post-therapy in responsive patients. The blood serum of RB patients only displayed low-to-non-detectable and therapy-independent TFF1 levels. The study suggests TFF1 expression in AH is a reliable biomarker, aiding RB diagnosis and treatment assessment and highlights its potential for non-invasive RB therapy monitoring. Effective management of retinoblastoma (RB), the most prevalent childhood eye cancer, depends on reliable monitoring and diagnosis. A promising candidate in this context is the secreted trefoil family factor peptide 1 (TFF1), recently discovered as a promising new biomarker in patients with a more advanced subtype of retinoblastoma. The present study investigated TFF1 expression within aqueous humor (AH) of enucleated eyes and compared TFF1 levels in AH and corresponding blood serum samples from RB patients undergoing intravitreal chemotherapy (IVC). TFF1 was consistently detectable in AH, confirming its potential as a biomarker. Crucially, our data confirmed that TFF1-secreting cells within the tumor mass originate from RB tumor cells, not from surrounding stromal cells. IVC-therapy-responsive patients exhibited remarkably reduced TFF1 levels post-therapy. By contrast, RB patients' blood serum displayed low-to-undetectable levels of TFF1 even after sample concentration and no therapy-dependent changes were observed. Our findings suggest that compared with blood serum, AH represents the more reliable source of TFF1 if used for liquid biopsy RB marker analysis in RB patients. Thus, analysis of TFF1 in AH of RB patients potentially provides a minimally invasive tool for monitoring RB therapy efficacy, suggesting its importance for effective treatment regimens. [ABSTRACT FROM AUTHOR]

Objectives: Obstructive sleep apnea (OSA) is one of the most common chronic diseases. Trefoil factor family 3 (TFF3) peptides are secreted by major and minor salivary glands and may be involved in the pathogenesis of OSA. This study aimed to evaluate salivary TFF3 and flow rate between those with and without OSA. Material and methods: This was a prospective experimental study that enrolled patients with OSA and non‐OSA. Total unstimulated saliva was collected, the salivary flow rate was measured, and the TFF3 level was analyzed by using a modified sandwich enzyme‐linked immunosorbent assay. Baseline characteristics, TFF3 level, and salivary flow rate were compared between both groups. Factors associated with the TFF3 level and flow rate were computed by using multivariate linear regression analysis. Results: Twenty‐eight participants were recruited in the study: 20 patients with OSA (71.42%) and 8 non‐OSA as control. The TFF3 and salivary flow rates between both groups of non‐OSA versus OSA were comparable (TFF3 non‐OSA 61.06 vs. OSA 96.00 ng/mg; p =.276 and flow rate non‐OSA 0.40 vs. OSA 0.35 mL/min; p =.320). Factors associated with the TFF3 level were neck circumference with a negative coefficient of −16.419 (p =.042). For the salivary flow rate, only age was a significant factor with the coefficient of −0.013 (p =.044). Conclusions: TFF3 and salivary flow rate were comparable between patients with OSA and non‐OSA. The factor associated with TFF3 level was neck circumference, while age was negatively associated with the salivary flow rate in patients with OSA. [ABSTRACT FROM AUTHOR]

The study's goal is to appraise the immunological inflammatory marker Trefoil Factor 3, which interacts with thalassemia pathogenesis particularly following splenectomy, and may offer new therapy options for the illness and its repercussions. This is a case-control study design that included 60 patients identified as β-thalassemia major as participators in this study, in addition to 30 seemingly healthy subjects with age and sex close to the patients group who served as a control group. The participants were distributed into four groups: control group, splenectomized patients, non-splenectomized patients, and total patients. Suitable statistical techniques were employed to investigate the results. The study's findings demonstrated that there was a significance increase in the serum levels of TFF3 when comparing between (splenectomized, non-splenectomized and total patients) with healthy group (322.16±51.241, p-value=0.01, 317.20±42.449, p-value=0.01, 320±46.6, p-value=0.01), vs (309.38±21.94), respectively. Moreover, a comparison between splenectomized and non-splenectomized showed a significantly decrease in TFF3 (322.16±51.241) vs (317.20±42.449), (p-value=0.043).The presented study also revealed significant positive correlation between TFF3 level with ferritin, iron, total iron binding capacity, transferrin saturation, transferrin, fasting serum glucose, insulin and homeostasis model assessment-insulin resistance. Furthermore, unsaturated iron binding capacity and homeostasis model assessment-beta found a significant negative correlation with TFF3 level. High serum levels of TFF3 in beta thalassemia patients, especially in splenectomies patients, are downregulated by inflammatory cytokines, which are primarily regarded as traditional inflammatory cytokines and are related to insulin resistance. Hence, TFF3 level can serve as a potential predictive for the early detection of beta thalassemia in the development and progression of complications. [ABSTRACT FROM AUTHOR]

Objective: To investigate the value of diffusion-weighted imaging (DWI) combined with serum carcinoembryonic antigen (CEA), trefoil factor 1 (TFF1)and soluble epithelial cadherin (sE-cadherin) in differentiating benign and malignant breast masses. Methods: 81 patients with breast mass who were admitted to Guang ’anmen Hospital of Chinese Academy of Traditional Chinese Medicine from January 2020 to January 2022 were selected. All patients underwent DWI examination and standardized apparent diffusion coefficient (ADC) was recorded, the serum CEA, TFF1 and sE-cadherin levels were detected. The value of ADC combined with serum CEA, TFF1 and sE-cadherin in differentiating benign and malignant breast masses was analyzed based on the results of surgical pathology or hollow needle biopsy. Results: Pathological examination confirmed malignant breast mass with 29 cases (malignant group), and benign breast mass with 52 cases (benign group). Malignant breast mass showed low or equal signal shadow on T1WI, high or mixed signal on T2WI, and high signal shadow on DWI. The ADC value in the malignant group was lower than that in the benign group (P＜0. 05), and the serum CEA, TFF1 and sE-cadherin levels were higher than those in the benign group (P＜0. 05). The area under the curve of combined ADC value and serum CEA, TFF1 and sE-cadherin was 0. 869, which was higher than 0. 677, 0. 681, 0. 654 and0. 581 of single index. Conclusion: The DWI images of malignant breast masses show high signal shadow, and decrease of ADC value. Serum CEA, TFF1 and sE-cadherin levels increase in patients with malignant breast masses. The combination of ADC value and serum CEA, TFF1 and sE-cadherin can effectively identify the nature of breast masses. [ABSTRACT FROM AUTHOR]

Objective This article evaluates the salivary trefoil factor levels using enzyme-linked immunosorbent assay and clinical parameters in stage I to II periodontitis subjects. Materials and Method A total of 44 subjects with periodontitis and healthy periodontium were enrolled for the study as per the inclusion criteria. The subjects were selected and categorized as group A (control group) and group B (test group). Scaling was performed on healthy subjects at baseline and 1 month if necessary and scaling and root planing was performed for periodontitis subjects. Trefoil factor 3 (TFF3) levels was analyzed at first and post-nonsurgical periodontal therapy followed by clinical parameters, respectively. Statistical Analysis Inferential statistics were performed using independent t -test and repeated measures of analysis of variance (ANOVA) test. Independent t -test was used for the intergroup comparison of all the variables. Repeated measures of ANOVA test along with post hoc Bonferroni test was used for the intragroup comparison and the level of statistical significance was set at 0.001. Results Difference in TFF3 levels and clinical parameters was seen between groups A and B, which was statistically significant. Conclusion Within the constraints of the study, it can be stated that TFF3 is a relevant biomarker to determine the activity and association of periodontal and systemic diseases, gastrointestinal disorders, and inflammatory bowel diseases. [ABSTRACT FROM AUTHOR]

The article discusses the acceptability of nonendoscopic screening for Barrett esophagus (BE) in the population. BE is a precursor to esophageal adenocarcinoma (EAC), and early detection followed by endoscopic surveillance can reduce EAC incidence and mortality. The study conducted a survey in the Netherlands to assess the willingness of individuals to undergo screening using different modalities. The results showed a high proportion of individuals expressing a willingness to undergo screening, with the least invasive technology (breath analysis) being the most preferred. Anticipated discomfort was identified as a major barrier to participation. The study provides valuable insights for the implementation of nonendoscopic BE screening. [Extracted from the article]

Objective: To explore the diagnostic value of color Doppler ultrasound combined with serum carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125), thymidine kinase 1 (TK1) and trefoil factor 1 (TFF1) in breast cancer. Methods: 97 patients with breast cancer who were admitted to our hospital from January 2019 to January 2022 were retrospectively selected as the observation group, and 97 patients with benign breast lesions who were admitted during the same period were selected as the control group. All patients underwent color Doppler ultrasonography and serum CEA, CA125, TK1 and TFF1 detection. Ultrasonic characteristics and ultrasonic parameters [pulsatility index (PI), peak systolic velocity (PSV), resistance index (RI)] were compared in the two groups. Serum CEA, CA125, TK1 and TFF1 levels were compared in the two groups. The diagnostic value of color Doppler ultrasound combined with serum CEA, CA125, TK1 and TFF1 and its diagnostic value alone were analyzed by receiver operating characteristic(ROC) curve. Results: Compared with the control group, the unclear mass boundary, uneven internal echo, irregular shape and calcification ratio in the observation group were significantly increased(P<0.05). Compared with the control group, RI, PSV and PI in the observation group were significantly higher(P<0.05). The proportion of blood flow signal grade III in the observation group was significantly higher than that in the control group(P<0.05), and the proportion of blood flow signal grade 0 in the observation group was significantly lower than that in the control group(P<0.05). Compared with the control group, the serum CEA, CA125, TK1, TFF1 levels in the observation group were significantly higher (P<0.05). ROC curve found that the area under the curve (AUC) value, sensitivity and specificity of ultrasound diagnosis of breast cancer were 0.773, 76.30% and 78.40% respectively. The AUC value, sensitivity and specificity of CEA in the diagnosis of breast cancer were 0.774, 78.40% and 74.23% respectively. The AUC value, sensitivity and specificity of CA125 in diagnosing breast cancer were 0.824, 77.31% and 80.41% respectively. The AUC value, sensitivity and specificity of TK1 in diagnosing breast cancer were 0.818, 78.43% and 81.42% respectively. The AUC value, sensitivity and specificity of TFF1 in diagnosing breast cancer were 0.806, 78.42% and 77.31% respectively. The AUC value of color Doppler ultrasound combined with serum CEA, CA125, TK1, TFF1 in the diagnosis of breast cancer was 0.929, which was significantly better than that of each indicator used alone (P<0.05). Conclusion: Compared with the single application of various indicators, color Doppler ultrasound combined with serum CEA, CA125, TK1, TFF1 has a higher value in the diagnosis of breast cancer, which is helpful for the early screening of breast cancer. [ABSTRACT FROM AUTHOR]

Background: Distinguishing between a pathologic state and renal development is important in neonatology. Because the assessment of serum creatinine in neonates is not reliable, better biomarkers are needed. Trefoil factor 3 (TFF3) is proposed as a biomarker of kidney injury. The study aimed to assess its urinary concentration in healthy term and stable preterm neonates. Material and methods: The study included 80 term and 20 preterm neonates born in the Department of Perinatology of the University Clinical Hospital in Bialystok. Urine was obtained from the term neonates on the 1st day of life and from the preterm neonates on the 1st, 8th, 15th and 22nd day of life. The urinary concentration of TFF3 was determined using a commercially available immunoassay and was normalized for the urinary creatinine concentration (cr.). Results: The values of TFF3/cr. were higher in the preterm than in the term neonates (p < 0.05) (median (Q1–Q3): 1486.85 (614.92–3559.18) and 317.29 (68.07–671.40) ng/mg cr.). They did not differ in the subsequent days of the preterm neonates' lives. The ROC curve for TFF3/cr. in the preterm and term neonates showed AUC = 0.751 (cut-off value = 1684.25 ng/mg cr.). Conclusions: Prematurity is associated with higher urinary excretion of TFF3. Male gender is associated with an increased urinary TFF3 excretion in term neonates. [ABSTRACT FROM AUTHOR]

Intestinal trefoil factor 3 (TFF3) is a protein secreted by many cell types, and its serum and urine levels vary in patients with kidney disease. Therefore, the present study aimed to determine the diagnostic value of TFF3 in allogeneic kidney transplant patients included in the one-year follow-up. To analyze the influence of the diagnostic method used, we studied the type of biological material and the time elapsed since renal transplantation on the parameter's value. The study also aimed to investigate the relationship between TFF3 levels and creatinine and estimated glomerular filtration rate (eGFR) values in the serum and urine of the patients studied. The study used blood and urine samples from adult patients (n = 19) 24–48 h, 6 months, and 12 months after kidney transplantation. We collected one-time blood and urine from healthy subjects (n = 5) without renal disease. We applied immunoenzymatic ELISA and xMap Luminex flow fluorimetry to determine TFF3 in serum and urine. There was a significant difference in TFF3 levels in the serum of patients collected on the first one or two days after kidney transplantation compared to the control group (determined by ELISA and Luminex) and six months and one year after kidney transplantation (ELISA). We observed a correlation between creatinine concentration and urinary TFF3 concentration (ELISA and Luminex) and a negative association between eGFR and urinary (ELISA) and serum (Luminex) TFF3 concentration in patients on the first and second days after kidney transplantation. We noted significant correlations between eGFR and TFF3 levels in the serum and urine of patients determined by the two methods six months and one year after transplantation. In women, we observed that urinary TFF3 concentration increased significantly with increasing creatinine and that with increasing eGFR, urinary TFF3 concentration determined by two methods decreased significantly. In the present study, the choice of diagnostic method for the determination of TFF3 in serum and urine significantly affected the concentration of this biomarker. The values of this parameter determined by ELISA were higher than those assessed using the Luminex assay. Based on the presented results, we can conclude that TFF3 has great potential to monitor renal transplant patients. Determination of this protein in parallel with creatinine and eGFR levels in serum and urine may provide helpful diagnostic information. [ABSTRACT FROM AUTHOR]

Background The Coronavirus pandemic (COVID-19) curtailed endoscopy services, adding to diagnostic backlogs. Building on trial evidence for a non-endoscopic oesophageal cell collection device coupled with biomarkers (Cytosponge), an implementation pilot was launched for patients on waiting lists for reflux and Barrett's oesophagus surveillance. Aims (i) To review reflux referral patterns and Barrett's surveillance practices. (ii) To evaluate the range of Cytosponge findings and impact on endoscopy services. Design and methods Cytosponge data from centralized laboratory processing (trefoil factor 3 (TFF3) for intestinal metaplasia (IM), haematoxylin & eosin for cellular atypia and p53 for dysplasia) over a 2-year period were included. Results A total of 10 577 procedures were performed in 61 hospitals in England and Scotland, of which 92.5% (N  = 9784/10 577) were sufficient for analysis. In the reflux cohort (N  = 4074 with gastro-oesophageal junction sampling), 14.7% had one or more positive biomarkers (TFF3: 13.6% (N  = 550/4056), p53: 0.5% (21/3974), atypia: 1.5% (N  = 63/4071)), requiring endoscopy. Among samples from individuals undergoing Barrett's surveillance (N  = 5710 with sufficient gland groups), TFF3-positivity increased with segment length (odds ratio = 1.37 per cm (95% confidence interval: 1.33–1.41, P  < 0.001)). Some surveillance referrals (21.5%, N  = 1175/5471) had ≤1 cm segment length, of which 65.9% (707/1073) were TFF3 negative. Of all surveillance procedures, 8.3% had dysplastic biomarkers (4.0% (N  = 225/5630) for p53 and 7.6% (N  = 430/5694) for atypia), increasing to 11.8% (N  = 420/3552) in TFF3+ cases with confirmed IM and 19.7% (N  = 58/294) in ultra-long segments. Conclusions Cytosponge-biomarker tests enabled targeting of endoscopy services to higher-risk individuals, whereas those with TFF3 negative ultra-short segments could be reconsidered regarding their Barrett's oesophagus status and surveillance requirements. Long-term follow-up will be important in these cohorts. [ABSTRACT FROM AUTHOR]

Rationale: Chronic obstructive pulmonary disease (COPD) is a complex disease characterized by airway obstruction and accelerated lung function decline. Our understanding of systemic protein biomarkers associated with COPD remains incomplete. Objectives: To determine what proteins and pathways are associated with impaired pulmonary function in a diverse population. Methods: We studied 6,722 participants across six cohort studies with both aptamer-based proteomic and spirometry data (4,566 predominantly White participants in a discovery analysis and 2,156 African American cohort participants in a validation). In linear regression models, we examined protein associations with baseline forced expiratory volume in 1 second (FEV1) and FEV1/forced vital capacity (FVC). In linear mixed effects models, we investigated the associations of baseline protein levels with rate of FEV1 decline (ml/yr) in 2,777 participants with up to 7 years of follow-up spirometry. Results: We identified 254 proteins associated with FEV1 in our discovery analyses, with 80 proteins validated in the Jackson Heart Study. Novel validated protein associations include kallistatin serine protease inhibitor, growth differentiation factor 2, and tumor necrosis factor-like weak inducer of apoptosis (discovery β = 0.0561, Q = 4.05 × 10−10; β  = 0.0421, Q = 1.12 × 10−3; and β = 0.0358, Q = 1.67 × 10−3, respectively). In longitudinal analyses within cohorts with follow-up spirometry, we identified 15 proteins associated with FEV1 decline (Q < 0.05), including elafin leukocyte elastase inhibitor and mucin-associated TFF2 (trefoil factor 2; β = −4.3 ml/yr, Q = 0.049; β = −6.1 ml/yr, Q = 0.032, respectively). Pathways and processes highlighted by our study include aberrant extracellular matrix remodeling, enhanced innate immune response, dysregulation of angiogenesis, and coagulation. Conclusions: In this study, we identify and validate novel biomarkers and pathways associated with lung function traits in a racially diverse population. In addition, we identify novel protein markers associated with FEV1 decline. Several protein findings are supported by previously reported genetic signals, highlighting the plausibility of certain biologic pathways. These novel proteins might represent markers for risk stratification, as well as novel molecular targets for treatment of COPD. [ABSTRACT FROM AUTHOR]

Simple Summary: Proteomics is a discipline investigating the proteins present in a specific biological environment, aiming to understand better the processes that take place in specific districts but also aiming for the possible discovery of new biomarkers. Herein, the fecal proteome of healthy dogs and dogs suffering from different hepatobiliary disorders was investigated. The study highlighted qualitative and quantitative differences between the groups of patients under analysis, leading us in particular to hypothesize a possible role for proteins such as fibronectin, haptoglobin, and trefoil factor 2. The present results need to be further confirmed by other tests and studies, but the direction taken appears promising. In the present study, the fecal proteomes of clinically healthy dogs (HD = n. 10), of dogs showing clinical, ultrasonographic, and/or laboratory evidence of different hepatobiliary dysfunction (DHD = n. 10), and of dogs suffering from chronic hepatitis (CHD = n. 10) were investigated with an Ultimate 3000 nanoUPLC system, coupled to an Orbitrap Fusion Lumos Tribrid mass spectrometer. Fifty-two different proteins of canine origin were identified qualitatively in the three study groups, and quantitative differences were found in 55 proteins when comparing groups. Quantitatively, a total of 41 and 36 proteins were found differentially abundant in the DHD and CHD groups compared to the control HD, and 38 proteins resulted dysregulated in the CHD group as compared to the DHD group. Among the various proteins, differently abundant fecal fibronectin and haptoglobin were more present in the feces of healthy and DHD dogs than in chronic ones, leading us to hypothesize its possible diagnostic/monitoring role in canine chronic hepatitis. On the other hand, the trefoil factor 2 was increased in DHD dogs. Our results show that the analysis of the fecal proteome is a very promising field of study, and in the case of dogs suffering from different hepatobiliary disorders, it was able to highlight both qualitative and quantitative differences among the three groups included. Results need to be confirmed with western blotting and in further studies. [ABSTRACT FROM AUTHOR]

Objective: To explore the relationship between serum tumor abnormal protein(TAP), trefoil factor 3(TFF3) and the sensitivity and prognosis of containing oxaliplatin chemotherapy regimen in patients with advanced gastric cancer. Methods: 115 patients with advanced gastric cancer who were admitted to Affiliated Hospital of Hebei University from January 2017 to January 2020 were selected. All patients received containing oxaliplatin chemotherapy regimen treatment, and they were divided into sensitive group(47 cases)and drug-resistant group(68 cases) according to the efficacy. Serum TAP and TFF3 levels were detected before chemotherapy, and the value of TAP and TFF3 in predicting the efficacy of oxaliplatin chemotherapy in patients with advanced gastric cancer was analyzed by receiver operating characteristic(ROC) curve. After treatment of follow-up, Wilcoxon analysis was used to analyze the difference in the median OS survival time of patients with advanced gastric cancer with different serum TAP and TFF3 expression. Results: Serum TAP and TFF3 levels in the drug-resistant group were higher than those in the sensitive group(P＜0.05). TAP and TFF3 predicted the area under curve of containing oxaliplatin chemotherapy resistance of patients with advanced gastric cancer were 0.717 and 0.690, respectively,combined TAP and TFF3 predicted the area under curve of containing oxaliplatin chemotherapy resistance of patients with advanced gastric cancer was 0.801, which was higher than TAP and TFF3 alone detection. During follow-up, 2 cases were lost to follow-up, and 54cases died, the median OS survival time of patients with high level of TAP and high level of TFF3 and advanced gastric cancer were lower than those of patients with low level of TAP and low level of TFF3 and advanced gastric cancer(P＜0.05). Conclusion: Serum TAP and TFF3 levels were significantly higher in advanced gastric cancer patients who were resistant to containing oxaliplatin chemotherapy, and high levels of TAP and TFF3 were associated with a shorter median OS survival time in advanced gastric cancer patients, and the combined detection of serum TAP and TFF3 may predict chemotherapeutic responsiveness and prognosis in advanced gastric cancer patients. [ABSTRACT FROM AUTHOR]

Objective: To explore the relationship between serum tumor abnormal protein(TAP), trefoil factor 3(TFF3) and the sensitivity and prognosis of containing oxaliplatin chemotherapy regimen in patients with advanced gastric cancer. Methods: 115 patients with advanced gastric cancer who were admitted to Affiliated Hospital of Hebei University from January 2017 to January 2020 were selected. All patients received containing oxaliplatin chemotherapy regimen treatment, and they were divided into sensitive group(47 cases)and drug-resistant group(68 cases) according to the efficacy. Serum TAP and TFF3 levels were detected before chemotherapy, and the value of TAP and TFF3 in predicting the efficacy of oxaliplatin chemotherapy in patients with advanced gastric cancer was analyzed by receiver operating characteristic(ROC) curve. After treatment of follow-up, Wilcoxon analysis was used to analyze the difference in the median OS survival time of patients with advanced gastric cancer with different serum TAP and TFF3 expression. Results: Serum TAP and TFF3 levels in the drug-resistant group were higher than those in the sensitive group(P＜0.05). TAP and TFF3 predicted the area under curve of containing oxaliplatin chemotherapy resistance of patients with advanced gastric cancer were 0.717 and 0.690, respectively,combined TAP and TFF3 predicted the area under curve of containing oxaliplatin chemotherapy resistance of patients with advanced gastric cancer was 0.801, which was higher than TAP and TFF3 alone detection. During follow-up, 2 cases were lost to follow-up, and 54cases died, the median OS survival time of patients with high level of TAP and high level of TFF3 and advanced gastric cancer were lower than those of patients with low level of TAP and low level of TFF3 and advanced gastric cancer(P＜0.05). Conclusion: Serum TAP and TFF3 levels were significantly higher in advanced gastric cancer patients who were resistant to containing oxaliplatin chemotherapy, and high levels of TAP and TFF3 were associated with a shorter median OS survival time in advanced gastric cancer patients, and the combined detection of serum TAP and TFF3 may predict chemotherapeutic responsiveness and prognosis in advanced gastric cancer patients. [ABSTRACT FROM AUTHOR]

Background: Biomarkers are the molecules that help in evaluating the status of disease and the prognosis of treatment. One such molecule that gained popularity as a biomarker among chronic periodontitis patients in recent days is Trefoil Factor 3(TFF3). TFF3 was evaluated in saliva, but its clinical signi􀃶cance and correlation with periodontal pathogens among periodontitis patients have never been investigated. Material & Methods: Saliva and supra, infra gingival plaque samples were collected from 30 periodontitis and 30 nonperiodontitis individuals. Enzyme-linked immunosorbent assay was used to estimate the salivary levels of TFF3. The polymerase chain reaction was advocated for analyzing periodontal pathogens from plaque samples. Results: Reduced salivary TFF3 levels were observed in chronic periodontitis patients, with a negative correlation between several periodontal pathogens and TFF3 levels. Conclusion: Our study results suggest a negative correlation between in􀃸ammatory mediators and salivary TFF3 levels. Thus, the estimation of TFF3 can be considered as a potential biomarker in evaluating disease states among periodontitis patients. [ABSTRACT FROM AUTHOR]

Finger citron pickled products (FCPP), as folk remedies, are famous in southern China for protecting gastric mucosa. However, the gastric mucosa protection of FCPP has not been reported yet, and its effective mechanism is unclear. In this study, the protective mechanism of FCPP aqueous extract on gastric mucosa was investigated in vitro and in vivo for the first time, using human gastric mucosa epithelial cells (GES-1) and acute alcoholic gastric ulcer rat model respectively. Furthermore, we also investigated the main substances in the aqueous extract that exert gastroprotective activity using a GES-1 scratch test and basic chemical composition analysis. FCPP aqueous extract was found to play a protective and reparative role in GES-1 by promoting the secretion of trefoil factor thyroid transcription factor 2 (TFF2) and inhibiting the secretion of tumor necrosis factor-α (TNF-α) in cells damaged by alcohol. The ulcer index of gastric tissue induced by alcohol was significantly decreased (p < 0.01) after pretreatment with FCPP aqueous extract, indicating that FCPP aqueous extract had a good protective effect on the stomach mucosa. Moreover, FCPP aqueous extract could increase superoxide dismutase (SOD) activity and inhibit malondialdehyde (MDA) content, exhibiting good antioxidant capacity. Aqueous extract of FCPP could also effectively inhibit the increase of cytokines TNF-α, interleukin-1β (IL-1β) and interleukin-6 (IL-6) in serum of rats, and promote the increase of anti-inflammatory cytokines interleukin-10 (IL-10) to some extent. Furthermore, FCPP aqueous extract could inhibit the expression of nuclear factor kappa-B (NF-κB/P65) protein, caspase-1 protein and IL-1β protein in the gastric tissue of rats, while promoting the expression of IκBα protein, indicating that the gastric mucosa protection effects of FCPP aqueous extract were mainly dependent on the NF-κB/caspase-1/IL-1β axis. The polysaccharides in FCPP aqueous extract might be the main components that exerted gastroprotective activity, as demonstrated by GES-1 cell scratch assay. This study confirmed that FCPP aqueous extract presented promising potential in protecting gastric mucosa and avoiding gastric ulcers, which could provide an experimental basis for further utilizing the medicinal value and developing new products of FCPP. [ABSTRACT FROM AUTHOR]

Background: Epigenetic modifications exhibit promising evidence in the etiology and prognosis of important diseases such as inflammatory bowel diseases (IBD). In addition to complex factors involved in IBD, a trend toward better prognosis has been reported in older ages of disease onset, specifically in ulcerative colitis (UC). The gastrointestinal mucous layer is one of the important components that is disturbed in the disease course. The integrity of this layer is maintained with an anti-inflammatory factor called trefoil factors (TFF). We investigated the methylation status of the TFF1 gene in UC patients alongside with correlation of its alteration level with age of disease onset. Method: We analyzed the promoter methylation status of the TFF1 gene, using the real-time quantitative multiplex methylation specific PCR (QM-MSP). DNA was extracted from colorectal biopsies of 15 ulcerative colitis and 14 healthy controls. Correlation analysis was performed between unmethylated DNA level and age through the Pearson correlation coefficient (PPC) test and simple linear regression models. Results: Our data provided a significant positive correlation between age and TFF1 hypomethylation in ulcerative colitis patients. However, no significant difference was observed in overall TFF1 methylation status between ulcerative colitis patients and control subjects. Conclusion: This finding suggests the association between epigenetic upregulation of the TFF1 gene with disease mildness in older patients. [ABSTRACT FROM AUTHOR]

The clinical drugs for ulcerative colitis mainly affect the inflammatory symposiums with limited outcomes and various side effects. Repairing the damaged intestinal mucosa is a promising and alternative strategy to treat ulcerative colitis. Trefoil factor family 2 (TFF2) could repair the intestinal mucosa, however, it has a short half-life in vivo. To improve the stability of TFF2, we have prepared a new fusion protein TFF2-Fc with much stability, investigated the therapeutic effect of TFF2-Fc on ulcerative colitis, and further illustrated the related mechanisms. We found that intrarectally administered TFF2-Fc alleviated the weight loss, the colon shortening, the disease activity index, the intestinal tissue injury, and the lymphocyte infiltration in dextran sulfate sodium (DSS)-induced colitis mice. In vitro, TFF2-Fc inhibited Caco2 cells injury and apoptosis, promoted cellular migration, and increased the expression of Occludin and ZO-1 by activating P-ERK in the presence of H2O2 or inflammatory conditioned medium (LPS-RAW264.7/CM). Moreover, TFF2-Fc could reduce lipopolysaccharide (LPS)-induced production of inflammation cytokines and reactive oxygen species in RAW264.7 cells, and also inhibits the polarization of RAW264.7 cells to M1 phenotype by reducing glucose consumption and lactate production. Taken together, in this work, we have prepared a novel fusion protein TFF2-Fc, which could alleviate ulcerative colitis in vivo via promoting intestinal epithelial cells repair and inhibiting macrophage inflammation, and TFF2-Fc might serve as a promising ulcerative colitis therapeutic agent. [ABSTRACT FROM AUTHOR]

Cellmembranes formbarriers for molecule exchange between the cytosol and the extracellular environments. ßγ-CAT, a complex of pore-forming protein BmALP1 (two ßγ-crystallin domains with an aerolysin pore-forming domain) and the trefoil factor BmTFF3, has been identified in toad Bombina maxima. It plays pivotal roles, via inducing channel formation in various intracellular or extracellular vesicles, as well as in nutrient acquisition, maintaining water balance, and antigen presentation. Thus, such a protein machine should be tightly regulated. Indeed, BmALP3 (a paralog of BmALP1) oxidizes BmALP1 to form a water-soluble polymer, leading to dissociation of the ßγ-CAT complex and loss of biological activity. Here, we found that the B. maxima IgG Fc-binding protein (FCGBP), a wellconserved vertebrate mucin-like protein with unknown functions, acted as a positive regulator for ßγ-CATcomplex assembly. The interactions among FCGBP, BmALP1, and BmTFF3 were revealed by co-immunoprecipitation assays. Interestingly, FCGBP reversed the inhibitory effect of BmALP3 on the ßγ-CAT complex. Furthermore, FCGBP reduced BmALP1 polymers and facilitated the assembly of ßγ-CAT with the biological poreforming activity in the presence of BmTFF3. Our findings define the role of FCGBP in mediating the assembly of a poreforming protein machine evolved to drive cell vesicular delivery and transport. [ABSTRACT FROM AUTHOR]

Chronic stress induces depression- and anxiety-related behaviors, which are common mental disorders accompanied not only by dysfunction of the brain but also of the intestine. Activating transcription factor 4 (ATF4) is a stress-induced gene, and we previously show that it is important for gut functions; however, the contribution of the intestinal ATF4 to stress-related behaviors is not known. Here, we show that chronic stress inhibits the expression ofATF4 in gut epithelial cells. ATF4 overexpression in the colon relieves stress-related behavioral alterations in male mice, as measured by open-field test, elevated plus-maze test, and tail suspension test, whereas intestine-specific ATF4 knockout induces stress-related behavioral alterations in male mice. Furthermore, glutamatergic neurons are inhibited in the paraventricular thalamus (PVT) of two strains of intestinal ATF4-deficient mice, and selective activation of these neurons alleviates stress-related behavioral alterations in intestinal ATF4-deficient mice. The highly expressed gut-secreted peptide trefoil factor 3 (TFF3) is chosen from RNA-Seq data from ATF4 deletion mice and demonstrated decreased in gut epithelial cells, which is directly regulated by ATF4. Injection of TFF3 reverses stress-related behaviors in ATF4 knockout mice, and the beneficial effects of TFF3 are blocked by inhibiting PVT glutamatergic neurons using DREADDs. In summary, this study demonstrates the function of ATF4 in the gut--brain regulation of stress-related behavioral alterations, via TFF3 modulating PVT neural activity. This research provides evidence of gut signals regulating stress-related behavioral alterations and identifies possible drug targets for the treatment of stress-related behavioral disorders. [ABSTRACT FROM AUTHOR]

Changes in the gut microbiome are recognized as an important component in the development of obesity in both adults and children. Infant feeding type, which may have a long-term effect on the microbial community, is one of the key factors in the gut microbiome formation in the early postnatal period. Breastfeeding contributes to the formation of mucosal tolerance to the intestinal microbiota, while trefoil factors (TFF2 and TFF3) are important components of the mucosal barrier. The aim of this study was to evaluate the composition of the gut microbiota and blood levels of trefoil factors in obese children and adolescents, depending on their infant feeding type. The study included 93 non-obese children (Group 1) and 92 obese children (Group 2). Serum TFF2 and TFF3 levels were determined by enzyme immunoassay. The taxonomic composition of the fecal microbiome was analyzed by metagenomic sequencing of the 16S rRNA gene. In general, the taxonomic composition of the gut microbiota in Groups 1 and 2 was similar. However, Group 2 was characterized by a smaller representation of [Prevotella], Epulopiscium and Haemophilus and a greater of Clostridium and Catenibacterium. Neither obesity nor the infant feeding type affected serum TFF2 and TFF3 levels. However, the infant feeding had a long-term effect on the gut microbiota, although in Group 2 this effect was less pronounced. In Group 1, breastfeeding led to the formation of a total mucosal tolerance to the gut microbiome, which was not the case with mixed and bottle feeding. In Group 2, most of the "TFF–gut microbiome" correlations were positive, indicative of an unfavorable intestinal wall–microbiome interaction in obese children and adolescents. Thus, infant feeding type appears to be a weak but significant factor in the gut microbiome formation in children and adolescents, which also affects the formation of mucosal tolerance to the gut microbiota. [ABSTRACT FROM AUTHOR]

Aims: We conducted observational and Mendelian randomization (MR) analyses to explore the associations between blood proteins and risk of peripheral artery disease (PAD). Methods and results: The observational cohort analyses included data on 257 proteins estimated in fasting blood samples from 12 136 Swedish adults aged 55–94 years who were followed up for incident PAD via the Swedish Patient Register. Mendelian randomization analyses were undertaken using cis-genetic variants strongly associated with the proteins as instrumental variables and genetic association summary statistic data for PAD from the FinnGen study (11 924 cases and 288 638 controls) and the Million Veteran Program (31 307 cases and 211 753 controls). The observational analysis, including 86 individuals diagnosed with incident PAD during a median follow-up of 6.6-year, identified 13 proteins [trefoil factor two, matrix metalloproteinase-12 (MMP-12), growth differentiation factor 15, V-set and immunoglobulin domain-containing protein two, N-terminal prohormone brain natriuretic peptide, renin, natriuretic peptides B, phosphoprotein associated with glycosphingolipid-enriched microdomains one, C-C motif chemokine 15, P-selectin, urokinase plasminogen activator surface receptor, angiopoietin-2, and C-type lectin domain family five member A] associated with the risk of PAD after multiple testing correction. Mendelian randomization analysis found associations of T-cell surface glycoprotein CD4, MMP-12, secretoglobin family 3A member 2, and ADM with PAD risk. The observational and MR associations for T-cell surface glycoprotein CD4 and MMP-12 were in opposite directions. Conclusion: This study identified many circulating proteins in relation to the development of incident PAD. Future studies are needed to verify our findings and assess the predictive and therapeutic values of these proteins in PAD. Graphical abstract [ABSTRACT FROM AUTHOR]

Background: The current study aims to determine the expression of trefoil factor 2 (TFF2), trefoil factor 3 (TFF3), and adrenomedullin (ADM) in salivary samples of periodontitis patients with and without coronary heart disease (CHD). Methods: A total of 75 patients were selected based on the inclusion and exclusion criteria and divided into three groups of 25 patients each: generalized periodontitis (GP) only; GP+CHD; and CHD only. Demographic, periodontal, and cardiac parameters were recorded, and unstimulated saliva samples were collected and analyzed for the expression of TFF2, TFF3, and ADM. Results: Among the demographic variables, the means for age,weight, and body mass indexwere significantly different between the groups on statistical analysis. Plaque index, bleeding on probing, probing pocket depth, clinical attachment level, and the expression of TFF2 were highest in the GP+CHD group, and ADM was highest in the CHD group, with P values of < 0.01 as compared to the other groups. TFF2, TFF3, and ADM were also correlated with the demographic and periodontal parameters. Conclusions: The study demonstrates significantly elevated levels of TFF2 in CHD and GP patients, and a higher expression of ADM in CHD patients only, suggesting the possibility of an underlying inflammatory mechanism. [ABSTRACT FROM AUTHOR]

Background: Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy cancer among the malignancies of thyroid. Despite of wide usages of proteomics in PTC, the profile of acetylated proteins in PTC remains unsettled, which is helpful for understanding the carcinogenesis mechanism and identifying useful biomarkers for PTC. Methods: The surgically removed specimens of cancer tissues (Ca-T) and adjacent normal tissues (Ca-N) from 10 female patients pathological diagnosed as PTC (TNM stage III) were enrolled in the study. After preparing the pooled extracts of the whole proteins and the acetylated proteins from 10 cases, TMT labeling and LC/MS/MS methods were applied to the assays of global proteomics and acetylated proteomics separately. Bioinformatics analysis, including KEGG, gene ontology (GO) and hierarchical clustering were performed. Some differentially expressed proteins (DEPs) and differentially expressed acetylated proteins (DEAPs) were validated by individual Western blots. Results: Controlled with the normal tissues adjacent to the lesions, 147 out of 1923 identified proteins in tumor tissues were considered as DEPs in global proteomics, including 78 up-regulated and 69 down-regulated ones, while 57 out of 311 identified acetylated proteins in tumor tissues were DEAPs in acetylated proteomics, including 32 up-regulated and 25 down-regulated, respectively. The top 3 up- and down-regulated DEPs were fibronectin 1, KRT1B protein and chitinase-3-like protein 1, as well as keratin, type I cytoskeletal 16, A-gamma globin Osilo variant and Huntingtin interacting protein-1. The top 3 up- and down-regulated DEAPs were ribosomal protein L18a-like protein, alpha-1-acid glycoprotein 2 and eukaryotic peptide chain release factor GTP-binding subunit ERF3A, as well as trefoil factor 3, thyroglobulin and histone H2B. Functional GO annotation and KEGG pathway analysis based on the DEPs and DEAPs showed completely different changing pictures. Contrary to the top 10 up- and -down regulated DEPs, most of which were addressed in PTC and other types of carcinomas, changes of the majority DEAPs were not mentioned in the literatures. Conclusions: Taken the profiling of the global and acetylated proteomics together will provide more broad view of protein alterations on the carcinogenesis and new direction for selecting biomarker for diagnosis of PTC. [ABSTRACT FROM AUTHOR]

The lectin TFF2 belongs to the trefoil factor family (TFF). This polypeptide is typically co-secreted with the mucin MUC6 from gastric mucous neck cells, antral gland cells, and duodenal Brunner glands. Here, TFF2 fulfills a protective function by forming a high-molecular-mass complex with the MUC6, physically stabilizing the mucus barrier. In pigs and mice, and slightly in humans, TFF2 is also synthesized in the pancreas. Here, we investigated the murine stomach, pancreas, and duodenum by fast protein liquid chromatography (FPLC) and proteomics and identified different forms of Tff2. In both the stomach and duodenum, the predominant form is a high-molecular-mass complex with Muc6, whereas, in the pancreas, only low-molecular-mass monomeric Tff2 was detectable. We also investigated the expression of Tff2 and other selected genes in the stomach, pancreas, and the proximal, medial, and distal duodenum (RT-PCR analysis). The absence of the Tff2/Muc6 complex in the pancreas is due to a lack of Muc6. Based on its known motogenic, anti-apoptotic, and anti-inflammatory effects, we propose a protective receptor-mediated function of monomeric Tff2 for the pancreatic ductal epithelium. This view is supported by a report that a loss of Tff2 promotes the formation of pancreatic intraductal mucinous neoplasms. [ABSTRACT FROM AUTHOR]

The trefoil factor family (TFF) is a relatively new family of peptides. In some studies, an association between trefoil factors and inflammatory diseases of the nasal and paranasal sinuses has been suggested. However, it is still not clear whether there is a relationship between trefoil peptides and inflammation of the respiratory tract. The aims of this study are to determine the presence of TFF1, TFF2, and TFF3 in the nasal mucosa and investigate their relationships with inflammation by using rat models of various sinonasal inflammations. Nasal tampon, lipopolysaccharide, and ovalbumin were used to generate rat models of sinonasal inflammation, i.e., rhinosinusitis and allergic rhinitis. The study was conducted on seventy rats in seven groups, each with ten rats: four groups with rhinosinusitis, two groups with allergic rhinitis, and a control group. Histological evaluation of sinonasal mucosa from all rats was performed, and Trefoil factors were investigated using immunohistochemical methods. All three TFF peptides were detected in rat nasal mucosa by histological evaluation. No significant differences in the trefoil factor scores were observed among the study groups. A significant correlation between the TFF1 and TFF3 scores and loss of cilia was identified (p < 0.05). In conclusion, no direct relationship between sinonasal inflammation and TFF scores was observed. However, a possible association between the TFF and epithelial damage or regeneration in sinonasal inflammation can be suggested based on the correlation observed between the TFF1 and TFF3 scores and scores of cilia loss. [ABSTRACT FROM AUTHOR]

Toxin-like proteins and peptides of skin secretions from amphibians play important physiological and pathological roles in amphibians. βγ-CAT is a Chinese red-belly toad-derived pore-forming toxin-like protein complex that consists of aerolysin domain, crystalline domain, and trefoil factor domain and induces various toxic effects via its membrane perforation process, including membrane binding, oligomerization, and endocytosis. Here, we observed the death of mouse hippocampal neuronal cells induced by βγ-CAT at a concentration of 5 nM. Subsequent studies showed that the death of hippocampal neuronal cells was accompanied by the activation of Gasdermin E and caspase-1, suggesting that βγ-CAT induces the pyroptosis of hippocampal neuronal cells. Further molecular mechanism studies revealed that the pyroptosis induced by βγ-CAT is dependent on the oligomerization and endocytosis of βγ-CAT. It is well known that the damage of hippocampal neuronal cells leads to the cognitive attenuation of animals. The impaired cognitive ability of mice was observed after intraperitoneal injection with 10 μg/kg βγ-CAT in a water maze assay. Taken together, these findings reveal a previously unknown toxicological function of a vertebrate-derived pore-forming toxin-like protein in the nerve system, which triggers the pyroptosis of hippocampal neuronal cells, ultimately leading to hippocampal cognitive attenuation. [ABSTRACT FROM AUTHOR]