Search Results (95)

Lotus corniculatus L., also known as birdsfoot trefoil (BFT), is a perennial, non-bloating, temperate forage legume widely grown due to its accumulation of high levels of condensed tannins (CTs) in foliage. However, variations in the CT levels and other plant metabolites in BFT genotypes in response to environmental and yearly factors under field conditions remain largely unexplored. Here, we combine conventional CT quantification and metabolome profiling with high-resolution liquid chromatography–mass spectrometry (LC-MS) to understand how environmental factors impact CT and other metabolite profiles. Eight BFT genotypes grown in Kentville, Canada, and Rhode Island and Utah in the United States were investigated, revealing significant genotypic variations in soluble CT contents. The global metabolome profiles of the eight BFT genotypes clustered predominantly based on geographical location. These results demonstrate that geographical location strongly influences CT accumulation and metabolome composition, offering potential for selecting genotypes adapted to specific environments. Our findings provide an opportunity for targeted breeding strategies to optimize CT levels, improve forage quality, and enhance stress resilience in birdsfoot trefoil. Full article

Phosphorus deficiency significantly limits soybean production across 74% of China’s arable land. This study investigated the molecular mechanisms enabling soybean to access insoluble phosphorus through transcriptome sequencing of the Heinong 48 variety across four developmental stages (Trefoil, Flower, Podding, and Post-podding). RNA-Seq analysis identified 2755 differentially expressed genes (DEGs), with 2506 up-regulated and 249 down-regulated genes. Notably, early developmental stages showed the most substantial transcriptional reprogramming, with 3825 DEGs in the Trefoil stage and 10,660 DEGs in the Flower stage, compared to only 523 and 393 DEGs in the Podding and Post-podding stages, respectively. Functional enrichment analysis revealed 44 significantly enriched GO terms in the Trefoil stage and 137 in the Flower stage, with 13 GO terms shared between both stages. KEGG pathway analysis identified 8 significantly enriched pathways in the Trefoil stage and 21 in the Flower stage, including key pathways related to isoflavonoid biosynthesis, alpha-linolenic acid metabolism, and photosynthesis. Among 87 differentially expressed transcription factors from 31 families, bHLH (8.08%), bZIP (7.18%), and WRKY (5.94%) were most prevalent. These findings provide genetic targets for developing soybean varieties with improved phosphorus acquisition capacity, potentially reducing fertilizer requirements and supporting more sustainable agricultural practices. Full article

The mechanisms involved in the regeneration of biliary epithelial cells (BECs) after liver injury remain unclear. In this study, we employed KRT19Cre^ERT/LSL-tdTomato (KT) mice and KT/TFF1KO mice to clarify the regeneration and cell fate of BECs via lineage tracing. Tamoxifen (TAM) was administered to the mice to label cytokeratin 19 (CK19)-positive BECs. The mice were subsequently fed a choline-deficient, ethionine-supplemented (CDE) diet for four weeks, after which the mouse livers were analyzed. Whereas the proportion of tdTomato⁺ cells in CK19-positive BECs decreased in the KT mice, it remained high in the KT/TFF1KO mice. Then, we analyzed hepatic progenitor cells (HPCs), the possible source of BECs. Although tdTomato-labeled HPCs were rarely found in the pretreatment mice, they were frequently found in the KT/TFF1KO mice after the CDE diet, suggesting the dedifferentiation of tdTomato-labeled BECs to HPCs. These results indicate not only that the loss of TFF1 accelerates the dedifferentiation of BECs into HPCs but also that HPCs are the source of BECs in TFF1KO mice. In addition, tdTomato-labeled HNF4α-positive hepatocytes were frequently found in the KT/TFF1KO mice, revealing the transdifferentiation of BECs to hepatocytes. The role of TFF1 as an inducer of biliary differentiation might be useful in the treatment of patients with hepatic or biliary dysfunction. Full article

Background and Objectives: The long-term renal and cardiovascular effects of neonatal acute kidney injury (AKI) in preterm infants remain unclear. This study investigated whether neonatal AKI leads to persistent subclinical kidney injury and blood pressure changes in school-aged children born preterm. Methods: In this prospective cohort, preterm-born children (≤35 weeks’ gestation) with (n = 19) and without (n = 38) neonatal AKI were evaluated at 7–12 years. A term-born control group (n = 44) was included for biomarker comparison. Assessments included perinatal data, anthropometry, office and ambulatory blood pressure monitoring (ABPM), and renal ultrasonography. Kidney function was evaluated using serum creatinine (sCr), cystatin C, and estimated glomerular filtration rate (eGFR). Tubular injury was assessed using urinary kidney injury molecule-1/Cr (KIM-1/Cr), neutrophil gelatinase-associated lipocalin/Cr (NGAL/Cr), and trefoil factor 3/Cr (TFF3/Cr) ratios, as well as serum TFF3. Results: Conventional kidney function markers were similar among groups. However, the AKI group had higher serum cystatin C, lower cystatin C–based eGFR, and elevated urinary KIM-1/Cr and NGAL/Cr compared to no-AKI and term controls. Serum TFF3 was also higher in the AKI group. ABPM revealed higher nocturnal systolic blood pressure and blood pressure load in the AKI group. Kidney size did not differ between preterm subgroups. Conclusions: Neonatal AKI in preterm infants is associated with subtle alterations and potential renal stress or injury at school age, detectable only with sensitive biomarkers and ABPM. Further prospective studies are needed to validate these biomarkers and determine their role in predicting long-term outcomes in preterm infants with neonatal AKI. Full article

Background/Objectives: Trefoil factor protein 3 (Tff3) is a small peptide known as an epithelial tissue-protective protein, and it is also identified as a novel participant in complex metabolic processes. In numerous mouse models of obesity, Tff3 has been found to be downregulated in the liver and its overexpression is associated with an improvement in metabolic parameters. These mouse models with metabolic phenotypes have a multigenic background, with numerous genes contributing to their phenotype. To elucidate the role of Tff3 protein in metabolic events, we developed a mouse model with Tff3 deficiency on a C57Bl6N background without other intrinsic mutations affecting metabolism. Methods: We investigated the effects of a high-fat diet (9 weeks) on the liver of Tff3 protein-deficient mice of both sexes and the corresponding wild type. We investigated the general metabolic status of the animals and analysed the expression of markers of relevant pathophysiological pathways in the liver. Results:Tff3-deficient mice had significantly lower body weight. They also had a comparable total liver fat content but it was distributed in small vesicles, indicating the protective effect of Tff3 deficiency. The results of molecular analysis showed no major gene expression changes in inflammation-, ER- and oxidative stress-, and lipid metabolism-related genes. Tff3^−/− males had reduced expression of Il1α and Cxcr7 genes in the liver and no global proteome changes; Tff3-deficient females had decreased expression of Irs2 and Atf4 genes and total proteome comparison showed decreased levels of proteins related to ribosome biosynthesis and the inhibition of acetylation. Conclusions: Our results demonstrate that Tff3 deficiency reduces lipid accumulation in the liver and we set the direction for further studies aimed at uncovering the exact molecular mechanisms in other organs. Furthermore, it emphasises the need to include both sexes in future research, as the observed phenotype differs significantly depending on sex. Full article

Trefoil factor 3 (TFF3) and epidermal growth factor (EGF) exert a promotive effect on the functions of intestinal epithelial cells and offer protection to the intestinal mucosa. Lactobacillus paracasei can ameliorate intestinal mucosal damage. In this study, pPG-pTFF3/27-2, pPG-pEGF/27-2, and pPG-pTE/27-2 were constructed to express porcine TFF3, EGF, and a fusion protein (pTE). Functional assays showed they promoted Immortalized Porcine Enterocyte Cell line J2 (IPEC-J2) proliferation and migration, with pTE having a greater migratory effect. In dextran sulfate sodium (DSS)-induced colitis mice, oral administration of pPG-pTE/27-2 reduced colitis, improved mucosal integrity, increased the expression of tight-junction proteins and the serum level of Interleukin-10 (IL-10), and decreased the levels of pro-inflammatory Tumor Necrosis Factor-α (TNF-α), Interleukin-6 (IL-6), and Interleukin-1β (IL-1β). These results imply that recombinant L. paracasei 27-2 strains engineered to express pTFF3 and pEGF represent a promising approach for augmenting intestinal epithelial cell function and facilitating mucosal restitution, and they possess significant potential in the treatment of intestinal mucosal injury and inflammatory bowel disease (IBD). Full article

Infecting humans with controlled doses of small intestinal helminths, such as human hookworm, is proposed as a therapy for the colonic inflammatory disease ulcerative colitis. Strengthening the colonic mucus barrier is a potential mechanism by which small intestinal helminths could treat ulcerative colitis. In this study, we compare C57BL/6 mice infected with the small intestinal helminth Heligmosomoides polygyrus and uninfected controls to investigate changes in colonic mucus. Histology, gene expression, and immunofluorescent analysis demonstrate that this helminth induces goblet cell hyperplasia, and an upregulation of mucin sialylation, and goblet-cell-derived functional proteins resistin-like molecule-beta (RELM-β) and trefoil factors (TFFs), in the colon. Using IL-13 knockout mice, we reveal that these changes are predominantly IL-13-dependent. The assessment of the colonic mucus microbiome demonstrates that H. polygyrus infection increases the abundance of Ruminococcus gnavus, a commensal bacterium capable of utilising sialic acid as an energy source. This study also investigates a human cohort experimentally challenged with human hookworm. It demonstrates that TFF blood levels increase in individuals chronically infected with small intestinal helminths, highlighting a conserved mucus response between humans and mice. Overall, small intestinal helminths modify colonic mucus, highlighting this as a plausible mechanism by which human hookworm therapy could treat ulcerative colitis. Full article

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. Full article

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. Full article

Purpose: To assess the possible impact of minor changes in fixation on wavefront measurements as a potential constraint in detecting subtle temporal variations in ocular wavefront error. Methods: Twelve healthy subjects with an average age of 36.3 ± 8.8 were instructed to put their heads in the aberrometer’s chin-rest and look at a fixation target that was embedded in the device. The fixation targets were readily observable to the participants without accommodation, thanks to the aberrometer’s Badal system. When each eye was staring at the target, its wavefront aberration was recorded three times and then averaged for further analysis. The averaged Zernike coefficients were rescaled to the smallest value of the maximum round pupil found among all eyes (4.41 mm), and this procedure was repeated for each target. Results: Alteration of the fixation targets caused changes to the Zernike coefficients of defocus (C(2,0)), vertical trefoil (C(3,–3)), vertical coma (C(3,–1)), horizontal coma (C(3,1)), oblique trefoil (C(3,3)), primary spherical aberration (C(4,0)), and secondary spherical aberration (C(6,0)), but the changes were not statistically significant. Nevertheless, an alteration in the target’s size and shape exhibited a significant correlation across all of the aforementioned coefficients in both eyes (p < 0.05). The total RMS of aberrations and the RMS of the spherical-like aberrations were both lowest while choosing the larger Maltese cross, and the bigger E-letter minimized the RMS of HOA and comatic aberrations. Conclusion: The aberrometric changes occur as a consequence of altering the fixational gaze and are within the range of the changes found after performing a near-vision task, so they might potentially act as a confounding factor when attempting to identify such small variations in the ocular wavefront. Using a smaller E-letter (5 arcmin) as an internal fixation target resulted in the least standard deviation of measurements, fixational stability, and higher accuracy in ocular wavefront measurements. Full article

The term “inflammatory bowel disease” (IBD) describes a class of relapse-remitting conditions that affect the gastrointestinal (GI) tract. Among these, Crohn’s disease (CD) and ulcerative colitis (UC) are two of the most globally prevalent and debilitating conditions. Several articles have brought attention to the significant role that inflammation and oxidative stress cooperatively play in the development of IBD, offering a different viewpoint both on its etiopathogenesis and on strategies for the effective treatment of these conditions. Marine ecosystems may be a significant source of physiologically active substances, supporting the search for new potential clinical therapeutics. Based on this evidence, this review aims to comprehensively evaluate the activity of marine algae and deriving biomolecules in decreasing pathological features of CD and UC. To match this purpose, a deep search of the literature on PubMed (MEDLINE) and Google Scholar was performed to highlight primary biological mechanisms, the modulation of inflammatory and oxidative stress biochemical parameters, and potential clinical benefits deriving from marine species. From our findings, both macroalgae and microalgae have shown potential as therapeutic solutions for IBD due to their bioactive compounds and their anti-inflammatory and antioxidant activities which are capable of modulating markers such as cytokines, the NF-κB pathway, reactive oxidative and nitrosative species (ROS and RNS), trefoil factor 3 (TFF3), lactoferrin, SIRT1, etc. However, while we found promising preclinical evidence, more extensive and long-term clinical studies are necessary to establish the efficacy and safety of marine algae for IBD treatment. Full article

Background: Barrett’s esophagus (BE) is a pre-neoplastic condition associated with an increased risk of esophageal adenocarcinoma (EAC). The accurate diagnosis of BE and grading of dysplasia can help to optimize the management of patients with BE. However, BE may be missed and the accurate grading of dysplasia based on a routine histology has a considerable intra- and interobserver variability. Thus, well-defined biomarker testing remains indispensable. The aim of our study was to identify routinely applicable and relatively specific biomarkers for an accurate diagnosis of BE, as well as determining biomarkers to predict the risk of progression in BE–dysplasia. Methods: Retrospectively, we performed immunohistochemistry to test mucin 2(MUC2), trefoil factor 3 (TFF3), p53, p16, cyclin D1, Ki-67, beta-catenin, and minichromosome maintenance (MCM2) in biopsies. Prospectively, to identify chromosomal alterations, we conducted fluorescent in situ hybridization testing on fresh brush samples collected at the time of endoscopy surveillance. Results: We discovered that MUC2 and TFF3 are specific markers for the diagnosis of BE. Aberrant expression, including the loss and strong overexpression of p53, Ki-67, p16, beta-catenin, cyclin D1, and MCM2, was significantly associated with low-grade dysplasia (LGD), high-grade dysplasia (HGD), and EAC histology, with a relatively high risk of neoplastic changes. Furthermore, the aberrant expressions of p53 and p16 in BE-indefinite dysplasia (IND) progressor cohorts predicted the risk of progression. Conclusions: Assessing the biomarkers would be a suitable adjunct to accurate BE histology diagnoses and improve the accuracy of BE–dysplasia grading, thus reducing interobserver variability, particularly of LGD and risk prediction. Full article

SeviL, a galactoside-binding lectin previously isolated from the mussel Mytilisepta virgata, was demonstrated to trigger apoptosis in HeLa ovarian cancer cells. Here, we show that this lectin can promote the polarization of macrophage cell lines toward an M1 functional phenotype at low concentrations. The administration of SeviL to monocyte and basophil cell lines reduced their growth in a dose-dependent manner. However, low lectin concentrations induced proliferation in the RAW264.7 macrophage cell line, which was supported by the significant up-regulation of TOM22, a component of the mitochondrial outer membrane. Furthermore, the morphology of lectin-treated macrophage cells markedly changed, shifting from a spherical to an elongated shape. The ability of SeviL to induce the polarization of RAW264.7 cells to M1 macrophages at low concentrations is supported by the secretion of proinflammatory cytokines and chemokines, as well as by the enhancement in the expression of IL-6- and TNF-α-encoding mRNAs, both of which encode inflammatory molecular markers. Moreover, we also observed a number of accessory molecular alterations, such as the activation of MAP kinases and the JAK/STAT pathway and the phosphorylation of platelet-derived growth factor receptor-α, which altogether support the functional reprogramming of RAW264.7 following SeviL treatment. These results indicate that this mussel β-trefoil lectin has a concentration-dependent multifunctional role in regulating cell proliferation, phenotype, and death in macrophages, suggesting its possible involvement in regulating hemocyte activity in vivo. Full article

Retinoblastoma (RB) is the most common malignant intraocular tumor in early childhood. Gene expression profiling revealed that the gastric inhibitory polypeptide receptor (GIPR) is upregulated following trefoil factor family peptide 1 (TFF1) overexpression in RB cells. In the study presented, we found this G protein-coupled transmembrane receptor to be co-expressed with TFF1, a new diagnostic and prognostic RB biomarker for advanced subtype 2 RBs. Functional analyses in two RB cell lines revealed a significant reduction in cell viability and growth and a concomitant increase in apoptosis following stable, lentiviral GIPR overexpression, matching the effects seen after TFF1 overexpression. In chicken chorioallantoic membrane (CAM) assays, GIPR-overexpressing RB cells developed significantly smaller CAM tumors. The effect of GIPR overexpression in RB cells was reversed by the GIPR inhibitor MK0893. The administration of recombinant TFF1 did not augment GIPR overexpression effects, suggesting that GIPR does not serve as a TFF1 receptor. Investigations of potential GIPR up- and downstream mediators suggest the involvement of miR-542-5p and p53 in GIPR signaling. Our results indicate a tumor suppressor role of GIPR in RB, suggesting its pathway as a new potential target for future retinoblastoma therapy. Full article

Spatial aspects of visual performance are usually evaluated through visual acuity charts and contrast sensitivity (CS) tests. CS tests are generated by vanishing the contrast level of the visual charts. However, the quality of retinal images can be affected by both ocular aberrations and scattering effects and none of those factors are incorporated as parameters in visual tests in clinical practice. We propose a new computational methodology to generate visual acuity charts affected by ocular scattering effects. The generation of glare effects on the visual tests is reached by combining an ocular straylight meter methodology with the Commission Internationale de l’Eclairage’s (CIE) general disability glare formula. A new function for retinal contrast assessment is proposed, the subjective straylight function (SSF), which provides the maximum tolerance to the perception of straylight in an observed visual acuity test. Once the SSF is obtained, the subjective straylight index (SSI) is defined as the area under the SSF curve. Results report the normal values of the SSI in a population of 30 young healthy subjects (19 ± 1 years old), a peak centered at SSI = 0.46 of a normal distribution was found. SSI was also evaluated as a function of both spatial and temporal aspects of vision. Ocular wavefront measures revealed a statistical correlation of the SSI with defocus and trefoil terms. In addition, the time recovery (TR) after induced total disability glare and the SSI were related; in particular, the higher the RT, the greater the SSI value for high- and mid-contrast levels of the visual test. No relationships were found for low contrast visual targets. To conclude, a new computational method for retinal contrast assessment as a function of ocular straylight was proposed as a complementary subjective test for visual function performance. Full article