Search Results (1,641)

Breast cancer is a significant cause of cancer-related mortality among women around the globe, underscoring the need for early and accurate diagnosis. Typically, histopathological analysis of biopsy slides is utilized for tumor classification. However, it is labor-intensive, subjective, and often affected by inter-observer variability. Therefore, this study explores a deep learning-based, multi-class classification framework for distinguishing breast cancer subtypes using convolutional neural networks (CNNs). Unlike previous work using the popular BreaKHis dataset, where binary classification models were applied, in this work, we differentiate eight histopathological subtypes: four benign (adenosis, fibroadenoma, phyllodes tumor, and tubular adenoma) and four malignant (ductal carcinoma, lobular carcinoma, mucinous carcinoma, and papillary carcinoma). This work leverages transfer learning with ImageNet-pretrained ResNet architectures (ResNet-18, ResNet-34, and ResNet-50) and extensive data augmentation to enhance classification accuracy and robustness across magnifications. Among the ResNet models, ResNet-50 achieved the best performance, attaining a maximum accuracy of 92.42%, an AUC-ROC of 99.86%, and an average specificity of 98.61%. These findings validate the combined effectiveness of CNNs and transfer learning in capturing fine-grained histopathological features required for accurate breast cancer subtype classification. Full article

The human airway surface is covered by a mucus layer composed primarily of the mucins MUC5AC and MUC5B. Excessive mucin production and secretion by airway epithelial cells in patients with asthma result in airway obstruction and worsened asthma symptoms. This study investigated the effects of liquiritin, a widely used flavonoid, on intracellular and secreted MUC5AC and MUC5B levels in the NCI-H292 human airway epithelial cell line. Liquiritin treatment suppressed both mucin types in a dose-dependent manner, accompanied by decreased activity of extracellular signal-regulated kinase (ERK) and p38. The effect of liquiritin was further examined in cells stimulated with phorbol 12-myristate 13-acetate (PMA) to induce excessive mucin production and secretion. Liquiritin dose-dependently reduced PMA-induced increases in intracellular and secreted MUC5AC and MUC5B levels as well as PMA-induced ERK and p38 activity. Overall, these results suggest that liquiritin reduces intracellular and secreted MUC5AC and MUC5B levels by suppressing the ERK and/or p38 signaling pathway. Full article

Human milk, especially colostrum, is a biologically complex fluid with potent protective properties against gastrointestinal disturbances in infants. Among intestinal protozoa transmitted via the fecal–oral route, this review focuses on Giardia lamblia and Entamoeba histolytica, as the protective role of milk-derived factors against these parasites is the most extensively documented. Its protective effects result from a wide range of bioactive components, including mucins, lactoferrin, human milk oligosaccharides, melatonin, and secretory IgA, which support the integrity of the intestinal barrier, regulate immune responses, and inhibit the adhesion and activity of pathogens. The composition of human milk can be influenced by maternal factors such as nutritional status, stress, sleep quality, and physical activity, which may modulate its immunological potential. Dietary intake of micronutrients, fermentable fibers, and fermented foods also appears to play a role in shaping the milk’s protective properties. This review discusses the molecular mechanisms by which selected milk components contribute to the defense against protozoan infections in early life and considers how maternal health and lifestyle may affect the effectiveness of these protective mechanisms. Full article

Environmental pollution with microplastics (MPs) can have a negative impact on human health. Certain findings point to the relationship between MP and the development of inflammatory bowel diseases (IBD). We investigated the effect of MP consumption on the severity of chronic colitis in male C57BL/6 mice. The MP effect was modeled by drinking water consumption with a suspension of 5 μm PS particles at a concentration of 10 mg/L replacement for 12 weeks. Chronic colitis was induced by three seven-day cycles of 1% DSS consumption (starting from the 8th, 29th and 50th days of the experiment). We investigated inflammatory infiltration, the goblet cell volume fraction and the highly sulfated and neutral mucins content in them, the endocrine cell number, the ulcerative-inflammatory process prevalence, changes in the gene’s expression encoding tight junction proteins, glycocalyx components proapoptotic factor Bax and proliferation marker Mki67 in the colon, and TNFα, IL-1β, IL-6 and IL-10 cytokines content in the serum. In healthy mice, MP did not cause pathological changes in the colon; however, indirect data indicate an increase in colon permeability. In chronic colitis, MP leads to higher prevalence of all pathological changes in general, and ulcers in particular, in a greater number of crypt abscesses and enteroendocrine cells. MP consumption leads to a more severe chronic colitis course. Full article

Aim: The aim of this study was to determine the age-specific characteristics of ovarian teratoma and associated malignancies. Methods: This retrospective single-centre cohort study included 2181 women with ovarian teratoma who underwent surgery at our institution between January 2008 and April 2019. Malignancies associated with ovarian teratoma were divided into immature teratoma, combined ovarian malignancy, and malignant transformation of mature cystic teratoma. The median patient age was 30 years (range, 7–82) and the median follow-up duration was 10 months (range, 0–152). Results: Most ovarian teratomas were detected incidentally, except in patients with abdominal pain under 20 years of age; torsion was significantly more common in this age group (p < 0.001). Tumours were larger in the younger age group (p < 0.01). The incidence of immature teratoma was 0.5% (n = 11), that of combined ovarian malignancy was 0.4% (n = 9), and that of malignant transformation was 0.4% (n = 9). The median patient age was 24.0 years for immature teratoma and 27.0 years for combined ovarian malignancy. The most common cell type was mucinous borderline tumour (55.6%, n = 5). The median patient age of malignant transformation was 33.0 years, and the most common cell type was carcinoid tumour (77.8%, n = 7). At our institution, the clinical manifestations of ovarian teratoma varied according to age group, with younger patients being more likely to be symptomatic and to have larger tumours and bilateral tumours. Although there was no statistically significant relationship between age and associated malignancy (p = 0.442), most of the malignancies associated with ovarian teratoma were found in childbearing age, not in older age. Conclusions: Given the possible associated malignancy with ovarian teratoma, surgeons should perform detailed preoperative evaluations, avoid intraoperative spillage, and perform intraoperative frozen biopsy when appropriate. Full article

Background: Despite escalating global pollution from microplastics (MPs) and the concurrent surge in high-fat food consumption, the health impacts of MP exposure on individuals under different dietary patterns remain poorly understood. Methods: This study investigated the differential effects of environmentally relevant concentrations of polystyrene microplastics (5 μm, 8 mg/kg) on gut barrier function in mice fed either a normal chow diet (CD) or a high-fat diet (HFD). Results: Key findings revealed that, in HFD-fed mice, MP exposure significantly reduced (p < 0.05) the transcriptional levels of genes encoding the tight junction proteins (ZO-1, Occludin, and Claudin-1), as well as the mucin protein Muc-2, accompanied by decreased protein expression levels of these markers in both colonic and ileal tissues. In contrast, no significant differences were observed in CD-fed mice exposed to MPs. Analysis of the gut microbiota and measurement of short-chain fatty acid (SCFA) metabolites showed that MPs induced significant alterations in the composition and diversity indices of the gut microbiota, along with a marked decrease (p < 0.05) in the levels of the characteristic metabolite butyrate in HFD-fed mice. Conversely, butyrate levels remained unchanged in CD-fed mice following MP exposure. Quantitative PCR (qPCR) and immunofluorescence staining of colonic tissues demonstrated that MP exposure significantly downregulated (p < 0.05) both the transcription and protein expression of peroxisome proliferator-activated receptor γ (PPARγ) in HFD-fed mice. Again, no significant changes were detected in CD-fed mice. Conclusions: These results collectively indicate that the impact of microplastics on the intestinal barrier differs significantly between mice fed normal and high-fat diets. The gut microbiota and its metabolites, particularly butyrate, may play a critical role, possibly through modulating PPARγ signaling. This study contributes valuable insights into understanding the toxicity profiles of microplastics and establishing crucial links between dietary patterns and the health effects of emerging pollutants. Full article

Galectin-9 (Gal-9, LGALS9) is a member of the family of carbohydrate-binding lectins known as galectins. Galectins bind a diverse repertoire of galactose-bearing glycoprotein receptors expressed across multiple cell types. These interactions elicit a broad spectrum of pleiotropic effects important in both normal physiology and disease pathogenesis. Gal-9 contains two separate carbohydrate recognition domains with overlapping yet also divergent binding affinities for distinct glycostructures. This tandem repeat motif enables fine-tuning of its various biological functions. Additional control of Gal-9 activity is provided via multiple gene variants, protein isoforms, tissue distribution, and cell type-associated glycoprotein binding profiles. Within the tumor microenvironment, Gal-9 interacts with immune, non-immune, and cancer cells to influence malignant progression. Its binding of the premier immune checkpoint glycoreceptors, T-cell immunoglobulin and mucin-domain-containing-3 (TIM-3) and programmed cell death protein 1 (PD-1), places Gal-9 apart as a burgeoning target for immunotherapy. In this review, we delve into important aspects of Gal-9 immunobiology in tumorigenesis, including glycobiological and lineage-dependent functions. We further examine Gal-9 as a promising new glyco-immune checkpoint target for cancer therapy. Full article

Background/Objectives: PROX1 (prospero homeobox 1) is a transcription factor involved in lymphangiogenesis and cellular differentiation. Its role in cancer biology appears to be highly context-dependent, with it exhibiting both tumor-promoting and -suppressive functions across various malignancies. Nonetheless, the clinical significance of PROX1 expression in non-small cell lung cancer (NSCLC) remains poorly elucidated. The objective of this study is to evaluate the immunohistochemical expression of PROX1 in NSCLC, specifically in the adenocarcinoma and squamous cell carcinoma subtypes, and to assess its correlation with clinicopathologic features and overall survival (OS). Methods: This retrospective study included surgically resected specimens from 121 patients with histologically confirmed NSCLC. PROX1 expression was assessed via immunohistochemistry on formalin-fixed, paraffin-embedded specimens. Staining intensity (graded 0– National and Kapodistrian University of Athens 3) and the percentage of positive tumor cells were recorded. Correlations with histological subtype, tumor characteristics, and OS were analyzed using chi-square tests, one-way ANOVA, and Kaplan–Meier survival analysis with log-rank testing. Results: Low PROX1 intensity (level 1) was significantly associated with P63 positivity (p = 0.028), while high PROX1 intensity (level 3) correlated with nodal metastasis to station 3 (S3+) (p = 0.025). Additionally, alveolar-pattern adenocarcinomas exhibited intermediate PROX1 expression (26–50%) (p = 0.010). Although PROX1 positivity did not differ among mucinous and non-mucinous adenocarcinomas (p = 0.152), its distribution across defined expression subgroups was statistically significant (p = 0.002). Tumors with low PROX1 expression (0–24%) were associated with a larger maximum tumor diameter (p = 0.026). PROX1 expression was not independently associated with OS (p > 0.05). Factors significantly associated with improved survival included an age < 50 years, female sex, the absence of necrosis, fewer than 10 positive lymph nodes, a lymph node ratio < 0.5, and the absence of extensive nodal involvement in stations 5, 10, 11, and 12. Conclusions: Although PROX1 expression is variably associated with specific histologic subtypes and nodal metastases in NSCLC, it does not independently predict overall survival. Its expression patterns suggest a potential role in tumor differentiation and lymphatic spread. Further mechanistic and immunologic studies are warranted to elucidate the functional significance of PROX1 in lung cancer biology. Full article

Astringency, a complex oral sensation resulting from interactions between mucin and polyphenols, remains difficult to quantify in portable field settings. Therefore, quantifying the aggregation through interactions can enable the classification of the astringency intensity, and assessing the capillary action driven by the surface tension offers an effective approach for this purpose. This study successfully replicates tannic acid (TA)–mucin aggregation on a paper-based microfluidic chip and utilizes machine learning (ML) to analyze the resulting capillary flow dynamics. Aggregates formed by mixing mucin with TA solutions at three concentrations showed that higher TA levels led to greater aggregation, consequently reducing the capillary flow rates. The flow dynamics were consistently recorded using a smartphone mounted within a custom 3D-printed frame equipped with a motorized sample loading system, ensuring standardized experimental conditions. Among eight trained ML models, the support vector machine (SVM) demonstrated the highest classification accuracy at 95.2% in distinguishing the astringency intensity levels. Furthermore, fitting the flow data to a theoretical capillary flow equation allowed for the extraction of a single coefficient as an input feature, which achieved comparable classification performance, validating the simplified feature extraction strategy. This method was also feasible even with only a portion of the initial data. This approach is simple and cost-effective and can potentially be developed into a portable system, making it useful for field analysis of various liquid samples. Full article

Background: Pulmonary benign metastasizing leiomyoma (PBML) is a rare condition characterized by histologically benign smooth muscle tumors occurring at extrauterine sites, often in women with a history of uterine leiomyoma. While PBML generally exhibits indolent behavior, its pathogenesis, management, and malignant potential remain unclear. Methods: This study retrospectively analyzes the clinical characteristics, imaging features, diagnostic approaches, pathological findings, treatment strategies, and outcomes of seven patients with PBML treated at our institution between January 2016 and May 2025. Results: Seven patients were included, with a mean age at diagnosis of 48.9 ± 5.6 years. Two patients presented with respiratory symptoms. Imaging revealed multiple bilateral pulmonary nodules in four patients and solitary nodules in three. Six patients were diagnosed via video-assisted thoracoscopic surgery, and one through computed tomography-guided percutaneous biopsy. Immunohistochemistry revealed positivity for SMA and Desmin in all cases, ER in six, and PR in five, with the Ki-67 labeling index ≤3% in six patients. One patient had a coexisting in situ mucinous adenocarcinoma within the PBML lesion. All had a history of uterine leiomyoma. After diagnosis, one patient received hormonal therapy, and another underwent right adnexectomy. The remaining patients were managed with surveillance without additional treatment. During follow-up, one patient developed distant organ metastasis. Conclusions: PBML is a rare, typically indolent condition with potential for metastasis. Accurate diagnosis relies on imaging, histopathology, and immunohistochemistry. This study reports a unique case of PBML coexisting with intratumoral in situ mucinous adenocarcinoma, a previously unreported finding that may broaden the known histopathological spectrum. Full article

Mucinous ovarian carcinoma (MOC) represents a rare and biologically distinct subtype of ovarian cancer, characterized by poor response to standard platinum-based chemotherapy and a unique molecular profile, including frequent KRAS mutations and HER2 amplifications. Recent advancements in targeted therapy, such as HER2 inhibitors and KRAS^G12C inhibitors, offer promising avenues for personalized treatment. Immunotherapy, particularly checkpoint inhibitors, shows potential in tumors with high PD-L1 expression or tumor mutational burden. Novel strategies, including antibody–drug conjugates, synthetic lethality approaches, and Wnt/β-catenin pathway inhibitors, are reshaping the therapeutic landscape. Despite these developments, challenges such as intratumoral heterogeneity and therapy resistance persist, underscoring the need for innovative clinical trial designs and combination regimens. This review synthesizes the latest advancements in MOC therapies, highlighting opportunities for improved outcomes in this challenging malignancy. Full article

Protein Disulfide Isomerases (PDIs) are emerging targets in anticancer therapy, with several PDI inhibitors demonstrating anticancer efficacy in preclinical models. Research has largely focused on “canonical” PDIs, such as PDIA1, which contain CXXC active site motifs where C represents Cysteine. Canonical PDIs have well-studied, critical roles in forming, breaking, and exchanging/scrambling disulfide bonds during protein folding. In contrast, non-canonical PDIs, which harbor CXXS active site motifs, remain less well-studied despite their role as sensors or effectors of protein folding quality control during protein trafficking in the secretory pathway. Here, we provide a review of the literature relating to the non-canonical PDIs ERp44, AGR2, and AGR3, which have been identified as strong dependencies in specific cancer subtypes according to the DepMap database. The biological and biochemical functions of ERp44, AGR2, and AGR3 are discussed, highlighting the role of ERp44 in two mechanisms of protein folding quality control, AGR2 as a selective sensor of mucin protein misfolding, and a unique role for AGR3 in cilia. Finally, we discuss recent efforts to develop small molecule inhibitors of ERp44, AGR2, and AGR3 as tool compounds and experimental therapeutics. Full article

Objectives: Saccharomyces boulardii CNCM I-745, a probiotic yeast, is effectively used for the treatment of acute diarrhea as well as for the prevention and treatment of traveller‘s diarrhea and diarrhea under tube feeding. The underlying mechanisms are not fully elucidated. Both antitoxic and regulatory effects on the intestinal barrier, mediated either by the yeast or yeast-derived substrates, have been discussed. Methods: To examine the effects of Saccharomyces boulardii released substrates (S.b.S) on gastrointestinal (GI) barrier function, a murine small intestinal organoid cell model under stress was used. Stress was induced by lipopolysaccharide (LPS) exposure or withdrawal of growth factors from cell culture medium (GF_Red). Stressed organoids were treated with S.b.S (200 µg/mL), and markers of GI barrier and inflammatory response were assessed. Results: GF_Red-induced stress was characterized by disturbances in selected tight junction (TJ) (p < 0.05), adherent junction (AJ) (p < 0.001), and mucin (Muc) formation (p < 0.01), measured by gene expressions, whereby additional S.b.S treatment was found to reverse these effects by increasing Muc2 (from 0.22 to 0.97-fold change, p < 0.05), Occludin (Ocln) (from 0.37 to 3.5-fold change, p < 0.0001), and Claudin (Cldn)7 expression (from 0.13 ± 0.066-fold change, p < 0.05) and by decreasing Muc1, Cldn2, Cldn5, and junctional adhesion molecule A (JAM-A) expression (all p < 0.01). Further, S.b.S normalized expression of nucleotide binding oligomerization domain (Nod)2- (from 44.5 to 0.51, p < 0.0001) and matrix metalloproteinase (Mmp)7-dependent activation (from 28.3 to 0.02875 ± 0.0044 ** p < 0.01) of antimicrobial peptide defense and reduced the expression of several inflammatory markers, such as myeloid differentiation primary response 88 (Myd88) (p < 0.01), tumor necrosis factor α (Tnfα) (p < 0.01), interleukin (IL)-6 (p < 0.01), and IL-1β (p < 0.001). Conclusions: Our data provide new insights into the molecular mechanisms by which Saccharomyces boulardii CNCM I-745-derived secretome attenuates inflammatory responses and restores GI barrier function in small intestinal organoids. Full article

IgG Fc binding protein (FcGBP) is a mucin-like protein that binds strongly to IgG and IgG–antigen complexes in intestinal mucus. FcGBP presence and its altered expression levels in meconium accumulating in the fetal intestine and amniotic fluid flowing in the intestine may provide new knowledge of the mechanisms responsible for the immune adaptation of the fetus to extrauterine life. FcGBP concentrations were measured by ELISA in the first-pass meconium and amniotic fluid samples collected from 120 healthy neonates delivered by either vaginal birth (n = 35) or cesarean section (n = 85) at 36 to 41 weeks gestation. The meconium FcGBP concentrations (405.78 ± 145.22 ng/g) decreased (r = −0.241, p = 0.007) over the course of 36 to 41 weeks gestation, but there were no significant changes (p > 0.05) in the amniotic fluid FcGBP (135.70 ± 35.83 ng/mL) in the same period. Both meconium and amniotic fluid FcGBP concentrations were higher (p < 0.05) in neonates delivered by cesarean section. Decreases in the meconium FcGBP concentrations correlated (r = −0.37, p = 0.027) with the gestational age in neonates delivered by vaginal birth but not in those delivered by cesarean section (p > 0.05). No association was found between the FcGBP concentrations in meconium and amniotic fluid and the birth weight (p > 0.05). With the development of the mucosal immune system in the fetal intestine over the course of the third trimester of gestation, the meconium FcGBP concentrations decrease. Increased FcGBP concentrations measured in the meconium and amniotic fluid of neonates delivered by cesarean section may possibly indicate altered intestinal mucosal function. Intrauterine growth is not associated with the intestinal mucosal barrier maturation involving FcGBP. Full article

Background: A dilated main pancreatic duct (MPD) ≥ 5 mm can be observed in main-duct IPMNs (MD-IPMN) and chronic pancreatitis (CP); however, distinguishing between the two differently treated diseases can be difficult. Cell-free (cf) DNA in MPD fluid obtained by EUS-guided FNA might help to distinguish MD-IPMN from CP. Methods: All patients with a dilated MPD ≥ 5 mm on EUS during the period of 1 June 2017 to 30 April 2024 were prospectively analysed in this single-centre study, with EUS-guided MPD fluid aspiration performed for suspected MD-IPMN or CP in patients who were suitable for surgery. Twenty-two known gastrointestinal cancer genes, including GNAS and KRAS, were analysed by deep targeted (dt) NGS. The results were correlated with resected tissue, biopsy, and long-term follow-up. Results: A total of 164 patients with a dilated MPD were identified, of which 30 (18.3%) underwent EUS-guided FNA, with 1 patient having a minor complication (3.3%). Twenty-two patients (mean MPD diameter of 12.4 (7–31) mm) with a definitive, mostly surgically confirmed diagnosis were included in the analysis. Only a fish-mouth papilla, which was present in 3 of 12 (25%) MD-IPMNs, could reliably differentiate between the two diseases, with history, symptoms, diffuse or segmental MPD dilation, presence of calcifications on imaging, cytology, and CEA in the ductal fluid failing to achieve differentiation. However, GNAS mutations were found exclusively in 11 of the 12 (91.6%) patients with MD-IPMN (p < 0.01), whereas KRAS mutations were identified in both diseases. Conclusions: GNAS testing by dtNGS in aspirated fluid from dilated MPD obtained by EUS-guided FNA may help differentiate MD-IPMN from CP for surgical resection. Full article