Search Results (109)

This study aimed to evaluate the protective effects of soluble dietary fiber (SDF) derived from Polygonatum cyrtonema Hua residues on cyclophosphamide (CTX)-induced intestinal injury in mice. A total of 60 C57BL/6 mice (6–8 weeks old; body weight, 23.8 ± 0.5 g) were randomly allocated to six groups (n = 10 per group): a control group (CON), a CTX model group (CTX), a levamisole-treated positive control group (PC), and low-, medium-, and high-dose SDF groups (125, 250, and 500 mg/kg body weight, respectively). Mice received oral administration of SDF or an equal volume of water for 21 consecutive days and were intraperitoneally injected with CTX (80 mg/kg body weight) on days 19–21 to induce intestinal injury. The results demonstrate that SDF possessed a porous, sponge-like network structure and comprised multiple monosaccharides. SDF intervention, particularly at medium and high doses, significantly attenuated CTX-induced body weight loss and immune organ atrophy; restored villus height and the villus-to-crypt ratio; increased the numbers of goblet cells and intraepithelial lymphocytes; elevated intestinal levels of sIgA, β-defensins, and lysozyme; and reduced serum levels of LPS, D-lactic acid, and DAO (p < 0.05). In conclusion, SDF derived from Polygonatum cyrtonema effectively mitigates CTX-induced intestinal injury by enhancing intestinal mucosal immunity and preserving intestinal barrier integrity, thereby highlighting its potential as a functional ingredient for promoting gut health. Full article

Background/Objectives: Cervical cancer remains a global health burden. The loop electrosurgical excision procedure (LEEP) is effective for cervical intraepithelial neoplasia. Positive margins often complicate decisions about repeat conization. HPV testing is standard in post-treatment surveillance, but its limited specificity shows the need for additional, cost-effective biomarkers. This study evaluated whether changes in systemic inflammatory indices—platelet-to-lymphocyte ratio (PLR), systemic inflammation response index (SIRI), and systemic immune-inflammation index (SII)—can predict residual high-grade lesions after incomplete excision. Methods: This multicenter retrospective study included 125 patients who underwent repeat surgery after LEEP due to positive margins. Changes in preoperative inflammatory indices (ΔPLR, ΔSIRI, ΔSII) between the first and second procedures were analyzed by the histopathological findings of the second surgery. Group differences were assessed using the Mann–Whitney U test, and receiver operating characteristic (ROC) analysis was used to evaluate discriminatory performance. Results: Significant differences were found in ΔPLR (p = 0.032) and ΔSII (p = 0.048) between patients with and without residual high-grade lesions or invasive cancer. ΔSIRI showed borderline significance (p = 0.050). For invasive cancer alone, ΔSIRI was significantly associated with malignancy (p = 0.035). ROC analysis showed modest predictive performance (AUC ≈ 0.60). Conclusions: Dynamic changes in PLR, SIRI, and SII may be as inexpensive adjunct biomarkers to support risk stratification after incomplete LEEP and can complement HPV testing in certain clinical settings. Full article

Celiac disease (CeD) is an immune-mediated enteropathy triggered by gluten in genetically susceptible individuals, with a heterogeneous clinical spectrum spanning classical gastrointestinal symptoms, extraintestinal manifestations, and subclinical forms. We synthesize contemporary epidemiology, immunopathogenesis, and the updated 2025 European Society for the Study of Coeliac Disease diagnostic framework. Adaptive responses to deamidated gliadin peptides presented by human leukocyte antigen (HLA)-DQ2/DQ8, together with interleukin-15-driven activation of intraepithelial lymphocytes (IELs), culminate in villous atrophy, crypt hyperplasia, and increased IELs. Serology centered on tissue transglutaminase immunoglobulin A (tTG-IgA) with total immunoglobulin A assessment remains first-line, complemented by standardized duodenal sampling (≥4 distal + 2 bulb biopsies) and selective HLA typing. The guidelines conditionally endorse a no-biopsy pathway for adults <45 years with tTG-IgA ≥10× upper limit of normal confirmed on a second sample, emphasizing shared decision-making and exclusion of red flags. We delineate differential diagnoses (tropical sprue, Crohn’s disease, common variable immunodeficiency, small intestinal bacterial overgrowth) and contrast CeD with non-celiac gluten sensitivity, which lacks villous atrophy, disease-specific serology, and HLA association. Emerging tools (immunohistochemistry, CD3/CD8/γδ IELs, video capsule endoscopy, confocal laser endomicroscopy) and the limitations of salivary/fecal assays are reviewed. Early detection improves quality of life and reduces healthcare utilization. Future directions include artificial intelligence-assisted imaging, molecular immunophenotyping, and non-dietary therapeutics. Full article

Background/Objectives: Tumour-infiltrating lymphocytes (TILs) significantly influence the prognosis of epithelial ovarian cancer (EOC). Advanced EOCs often cause neutrophilia, ascites, and malnutrition. The neutrophil-to-lymphocyte ratio (NLR) serves as a marker of systemic inflammation. This study investigated the prognostic significance of pre-treatment NLR and TILs in advanced EOCs. Methods: Overall, 101 advanced EOCs (stages III–IV, FIGO 2014) were treated between 2005 and 2020. Based on pathological findings, advanced EOCs were classified as having high or low TILs using CD8 and CD4 immunostaining. The tumour proportion score was calculated to determine PD-L1 expression. The number of marker-positive cells was counted using HALO. Progression-free survival and overall survival (OS) were compared between the high- and low-NLR groups based on TILs levels. Results: Clinicopathological characteristics, including age, FIGO stage, histological subtype, and postoperative residual disease, did not significantly differ among the four groups defined by NLR and intra-epithelial CD8+ TILs (CD8+ iTILs). Multivariate analysis of OS revealed that NLR and CD8+ iTILs were independent prognostic factors, and no correlation was observed between them. The 5-year OS rates were 82.2% in the low NLR–high CD8+ iTILs group (n = 25), 41.7% in the low NLR–low CD8+ iTILs group (n = 16), 47.2% in the high NLR–high CD8+ iTILs group (n = 34), and 26.0% in the high NLR–low CD8+ iTILs group (n = 26). In the low-NLR subgroup, OS was significantly prolonged in the high CD8+ iTILs group (p = 0.023). Conclusions: In advanced EOCs, the status of tumour-localised immunity and pre-treatment systemic inflammation influenced long-term prognosis. Full article

Histological healing is increasingly recognized as a sensitive marker of disease remission in ulcerative colitis (UC). However, the dynamics of mucosal T lymphocytes and proinflammatory cytokines during healing remain incompletely understood. In this paired, within-subject observational study (retrospective analysis of paired biopsies), colonic biopsy sets from 20 adult UC patients were analyzed during active inflammation and at a subsequent time point of histologic healing. Immunohistochemistry was performed for CD3, CD4, CD8, and IL-6. Lymphocyte densities were quantified in intraepithelial and lamina propria compartments, while IL-6 expression was scored semi-quantitatively. Histological activity was assessed using the Geboes score. Intraepithelial CD4⁺ T cells significantly decreased during histologic healing (mean 6.8 → 3.75 cells/100 epithelial cells, p < 0.05), whereas lamina propria CD4⁺ cells remained variably persistent, suggesting ongoing immune regulation. Intraepithelial CD8⁺ cells increased during remission, indicating a potential reparative or surveillance role. IL-6 expression markedly declined in epithelial and stromal compartments during healing, reflecting resolution of mucosal inflammation. Correlation analyses revealed enhanced coordination between CD4⁺ and CD8⁺ cells in the healing phase, consistent with immune homeostasis. Histologic healing in UC involves compartment-specific shifts in T lymphocyte populations and a marked reduction in IL-6 expression, reflecting coordinated immune regulation beyond clinical remission. These findings highlight the potential of combined cellular and cytokine biomarkers to monitor mucosal healing and guide immunomodulatory therapies. Full article

Food allergies are rising globally, posing a multifactorial public health challenge driven by complex interactions among diet, immune development, and environmental exposures. This review highlights emerging insights into the cellular and molecular mechanisms by which specific dietary components, particularly vitamin A, fibre, indole compounds, and proteins, promote intestinal homeostasis. These nutrients act through both microbiota-dependent and -independent pathways, primarily in the small intestine, enhancing epithelial barrier integrity and supporting tolerogenic immune responses. Two key signalling axes, mediated by retinoic acid (RA) and aryl hydrocarbon receptor (AhR) ligands, converge to regulate RORγt-expressing immune cells, including group 3 innate lymphoid cells, TCRγδ⁺CD8αα⁺ intraepithelial lymphocytes (IELs), and Th17 cells, which are essential for secondary lymphoid organ development and barrier reinforcement. RA and AhR also guide the homing and specialization of diverse regulatory T cell subsets and CD4⁺ IELs, which collectively sustain peripheral tolerance to dietary antigens. Recent findings implicate RORγt⁺ antigen-presenting cells in the induction of peripheral Tregs during early life, particularly at weaning, underscoring a critical window for tolerance establishment. Microbial metabolites and commensal-derived signals further shape these immune pathways, reflecting the intricate interplay between host, diet, and microbiota in the regulation of oral tolerance. Full article

Non-muscle invasive bladder cancer (NMIBC) accounts for the majority of bladder cancer diagnoses and remains a clinical challenge due to its high recurrence and progression rates despite intravesical Bacillus Calmette–Guérin (BCG) therapy. In recent years, tumor-infiltrating lymphocytes (TILs) have emerged as promising biomarkers, reflecting the interplay between the tumor and host immune system. However, the evidence regarding their prognostic and predictive role is still conflicting, largely due to methodological heterogeneity, lack of standardized evaluation criteria, and limited prospective validation. This narrative review summarizes the current knowledge on TILs in NMIBC, focusing on their compartmental distribution (stromal, intraepithelial, and tumor–stroma interface), compositional diversity (CD4⁺, CD8⁺, Treg, B cells), and spatial dynamics. Special attention is given to their role in predicting response to BCG immunotherapy, the contribution of tumor-associated macrophages and tertiary lymphoid structures, and the emergence of immune escape pathways, including Programmed Death-Ligand 1 (PD-L1) and the HLA-E/NKG2A axis. Advances in digital pathology, spatial transcriptomics, and integrated immunoscore models provide more accurate metrics compared to simple cell counts, highlighting the importance of functional and spatial signatures. Despite encouraging progress, TILs are not yet ready for routine incorporation into histopathological reporting. Future directions include standardized assessment, integration with molecular biomarkers, and prospective multicenter validation to enable their translation into risk stratification and personalized therapeutic decision-making. Full article

Antiretroviral therapy (ART) controls HIV-1 replication in people with HIV-1 (PWH), but intestinal integrity impairment persists and fuels microbial translocation and chronic immune activation, thus heightening the cardiovascular disease (CVD) risk. Here, we sought to identify novel immunological correlates of the HIV and CVD status in ART-treated PWH (HIV⁺; n = 42) and uninfected participants (HIV⁻; n = 40) of the Canadian HIV and Aging Cohort Study (CHACS), with/without subclinical coronary atherosclerotic plaques, measured by Coronary Computed Tomography Angiography as total plaque volume (TPV, mm³). PBMCs were analyzed by flow cytometry for the expression of T-cell lineage (CD45, CD3, CD4, CD8αα, CD8αβ, TCRαβ, TCRγδ), epithelial cell (EpCAM/CD326), activation (HLA-DR), and gut-homing/residency markers (CD69, CD196/CCR6, CD199/CCR9, CD49d/Itgα4, CD103/ItgαE, Itgβ7). Alterations in the CD3⁺ T-cell pool, such as increased frequencies of CD8⁺TCRαβ⁺ and TCRγδ⁺ cells, to the detriment of CD4⁺TCRαβ⁺ subsets, were associated with the HIV status. Also, CD4⁺ T-cells with CD326⁺CD69⁺CCR6⁺ItgαE⁺ and CCR6⁺Itgβ7⁻ phenotypes were increased in frequency in HIV⁺ vs. HIV⁻ participants, together with a decreased frequency of CD8⁺ T-cells with an intraepithelial lymphocyte (IEL)-like CD3⁺CD4⁻TCRαβ⁺TCRγδ⁻CD8αα⁺CD8αβ⁻ phenotype. Finally, multivariate logistic regression identified the frequency of ItgαE⁺CD8⁺, ItgαE⁻CD8⁺, CCR6⁺CD4⁺, and CCR6⁺Itgβ7⁻CD4⁺ T-cells as strong positive correlates of HIV status and atherosclerotic plaque in ART-treated PWH. Full article

Background: Celiac disease (CD) is a gluten-sensitive immune-related enteropathy of the small intestine characterized by villus atrophy, crypt hyperplasia, and increased intraepithelial lymphocytes (IELs). Objectives: To characterize the phenotype of IELs and immune cells of the lamina propria of small intestine control using immuno-oncology and immune-phenotype markers and test the most relevant marker, an immune checkpoint co-inhibitory receptor, leukocyte-associated immunoglobulin-like receptor 1 (LAIR1), in CD. Methods: Immunohistochemical analysis of CD3 (CD3E), CD4, CD8, CD103 (ITGAE), Granzyme B (GZMB), TCR beta (β), TCR delta (δ), CD56 (NCAM), CD16 (FCGR3A), LAIR1 (CD305), PD-L1 (CD274), PD1 (CD279), BTLA (CD272), TOX2, HVEM (TNFRSF14), CD163, HLA-DP-DQ-DR, IL4I1, and FOXP3 was performed using histological analysis. Gene expression analysis was performed using an independent dataset to expand and confirm the findings. Results: IELs exhibited a cytotoxic T-cell phenotype and were CD3+, CD8+, CD103+, TCR beta+, and LAIR1+. The lamina propria (LP) was abundant in CD163+, HLA-DP-DQ-DR+, BTLA+, PD-L1+, CD103+, CD56+, and LAIR1+ cells corresponding to macrophages and T- and B-lymphocytes. In CD, IELs and part of the inflammatory cells of the lamina propria cells were LAIR1+. CD was characterized by higher quantity of LAIR1+ IELs and LP immune cells than the small intestine control (p = 0.004). Higher intestinal lesions evaluated by Marsh scoring were correlated with higher LAIR1 (p < 0.001). Gene expression analysis confirmed the overexpression of the LAIR1 pathway in CD and highlighted BTLA. At the protein level, BTLA overexpression was confirmed in CD. Finally, as a proof-of-concept AI analysis, a convolutional neural network classified LAIR1-stained image patches between the three diagnoses of small intestine control, CD, and reactive tonsils with high accuracy (99.6%). Conclusions: IELs exhibit a cytotoxic T-cell phenotype and were found to be CD3+, CD8+, CD103+, TCR beta+, and LAIR1+ in the small intestine control. Increased numbers of LAIR1+ IELs and lamina propria immune cells characterize CD. Full article

Objective: This study aimed to identify risk factors associated with high-grade cervical intraepithelial neoplasia (CIN3+) in young adults with abnormal Pap smears. Methods: We performed a retrospective chart review of women ≤30 years who underwent loop electrosurgical excision procedure (LEEP) for abnormal Pap results (atypical squamous cells of undetermined significance [ASCUS] or higher), between 2012 and 2022 at Dongtan Sacred Heart Hospital. Clinical characteristics, including age, HPV infection, prior gynecologic surgery, pelvic inflammatory disease (PID), complete blood count, and Pap smear screening history were collected. Women with CIN3+ based on punch biopsy or LEEP were designated as CIN3+. Results: A total of 158 women underwent LEEP. Of these, 61.4% were diagnosed with CIN3+ and 8.2% with invasive cervical cancer. Independent predictors of CIN3+ included age >28 years, smoking, lack of regular Pap screening, and high-risk HPV infection. Subgroup analysis suggested age ≥28 years and neutrophil-to-lymphocyte ratio >2.12 were risk factors for invasive cervical cancer. Conclusions: Young Korean women with abnormal Pap smears and risk factors such as older age, smoking, high-risk HPV infection, and irregular screening histories are at increased risk for CIN3+. These findings highlight the importance of timely intervention; however, because our cohort included only women who underwent LEEP, it may represent a higher-risk subset and thus introduce selection bias. Validation in larger multicenter, prospective studies incorporating fertility and recurrence outcomes are needed before definitive recommendations can be made. Full article

Background: The quest for effective immunoenhancers is central to improving vaccine efficacy, especially against avian viruses such as Newcastle disease (ND) virus. Selenized polysaccharides integrate bioactive polysaccharides with selenium’s immunoenhancing properties while reducing selenium toxicity, making them promising candidates for the development of a novel vaccine immunoenhancer. Aim: This study aimed to develop an efficient selenized Brassica rapa L. polysaccharide (sBRP) and evaluate its potential to enhance the immunogenicity of a live-attenuated ND vaccine in poultry. Methods: Selenization was achieved via nitrite-assisted selenization of Brassica rapa L. polysaccharide (BRP). In vivo, 180 yellow-feathered broilers were divided into six groups: control (Con), vaccine-only (Vac), BRP (20 mg/kg), and low/medium/high-dose sBRP (sBRP-L/M/H: 5/10/20 mg/kg). On days 14 and 28, all groups except Con were vaccinated against ND via drinking water. Concurrently, the BRP and sBRP-L/M/H groups received their respective polysaccharides via oral gavage. Parameters assessed included immune organ indices, lymphocyte proliferation, serum antibody titers (HI), cytokine levels (IL-2/IL-6/IFN-γ), and densities of intestinal intraepithelial lymphocytes (IELs) and goblet cells (GCs). Results: sBRP exhibited a selenium content of 30.6 mg/g, with Se-O-C covalent modification confirmed. The sBRP-H group significantly enhanced immune organ indices, lymphocyte proliferation, Newcastle disease virus HI antibody titers, and serum IL-2/IL-6/IFN-γ levels. The sBRP-M group increased IEL and GC densities in the intestine. Conclusions: sBRP acts synergistically with the vaccine to enhance vaccine-induced cellular, humoral, and mucosal immunity, demonstrating promise as a novel oral vaccine immunoenhancer. Full article

Background: Cervical cancer remains a major global health burden, particularly in regions with limited early detection. The Loop Electrosurgical Excision Procedure (LEEP) is commonly used to diagnose and treat cervical intraepithelial neoplasia (CIN). The lymphocyte-to-monocyte ratio (LMR) is a potential biomarker for cancer risk stratification. It reflects immune function and tumor-related inflammation. Lower LMR values suggest reduced antitumor immunity and increased tumor-promoting inflammation, which are linked to cancer development and progression. This study examines relationships between preoperative LMR and histopathological outcomes after LEEP. Methods: This retrospective study included 374 patients undergoing the LEEP for cervical dysplasia. Preoperative LMR values were compared across four histopathological categories: negative, low-grade, high-grade lesions, and invasive carcinoma. The Kruskal–Wallis test assessed group differences, with Mann–Whitney U tests for pairwise comparisons. ROC curve analysis (n = 369) evaluated LMR’s diagnostic performance, and logistic regression evaluated its independent predictive value. Results: LMR significantly differed across cytological (p = 0.04) and histological groups (p = 0.036). Post hoc analysis revealed significantly lower LMR in invasive carcinoma versus low-grade lesions in cytology and for both low- and high-grade lesions in histology. ROC analysis yielded an AUC of 0.680. An LMR cutoff <4.49 showed 82.6% sensitivity and 50.0% specificity. Stricter cutoff (<3.89) increased specificity (66.8%) but decreased sensitivity (60.9%). Both had high negative predictive values (97.7% and 96.2%) but low positive predictive values (9.9% and 10.9%). Conclusions: LMR may serve as a complementary biomarker to predict higher-grade cervical lesions and help rule out invasive disease, aiding patient triage in resource-limited settings. Full article

Adenoma-like adenocarcinoma (ALAC) of the colon is a recently recognized histological subtype of colorectal adenocarcinoma, characterized by a villous architecture, low-grade cytologic atypia, and deceptive bland morphology despite its invasive potential, which can mimic non-invasive adenomas, leading to underdiagnosis in limited biopsy samples. Herein, we report the case of an 81-year-old male presenting with right-upper-quadrant pain that was found to have a hepatic abscess and a 4 cm villous lesion in the ascending colon. Histopathological examination of the right hemicolectomy specimen revealed a villous adenocarcinoma with invasion of the muscularis propria, consistent with adenoma-like adenocarcinoma. Isolated loss of PMS2 indicated a mismatch repair deficiency. However, adjuvant therapy was not indicated. The patient remained recurrence-free for three years, until he died from unrelated causes in the context of progressive frailty and comorbidities, with no evidence of cancer progression. This case highlights the diagnostic challenges posed by ALAC and underscores the importance of recognizing its distinct morphological features. Awareness of this entity is essential to avoid misclassification and ensure adequate treatment, especially given its typically favorable prognosis with low metastatic potential. Full article

An alternative fish feed (ALT) replacing 50% of the fishmeal with poultry byproduct meal and insect meal and total fish oil with microalgae, poultry, and salmon byproducts oils was tested for 300 days on 900 gilthead seabream (Sparus aurata) with an initial body weight of 17.1 ± 1.8 g (mean ± SD) of unselected (REF) and selected (HG) genotypes. Using in situ, histochemistry, and immunohistochemistry techniques, we assessed the immune response by characterizing IgT and IgM immunoglobulins, CD3ε⁺ T lymphocytes, and eosinophilic granular cells (EGCs) along the digestive system. IgT mRNA⁺ cells were concentrated in the second part of the digestive tract, while IgM⁺ predominated in the first and occasionally showed intraepithelial localization. CD3ε⁺ and EGCs were most prominent in the midgut. The diet affected IgT and IgM mRNA⁺ cells mainly in the initial part of the digestive tract. For CD3ε⁺, the diet only affected the initial and final parts, while the ALT diet increased EGC abundance across the middle compartments. Genetic selection had minimal effect on IgT⁺ and CD3ε⁺ cells, affecting only the first compartments. The REF group showed higher IgM⁺ cell abundance in specific regions, while EGCs differed between genotypes, favoring anterior accumulation in HG and ileocecal abundance in the REF group. Full article

Background: Olmesartan-induced enteropathy is a rare complication of a widely used angiotensin II receptor blocker. Patients usually present with chronic diarrhea and weight loss. Histologically, villous atrophy and intraepithelial lymphocyte infiltrates within the duodenum confirm the diagnosis. The prognosis is usually good after withdrawal of the offending drug. Case presentation: Here, we report the case of a 76-year-old woman who developed a severe form of Olmesartan-induced enteropathy complicated by acute kidney injury and acute recurrence after drug rechallenge. After definite cessation of the drug, the patient did not experience any gastrointestinal (GI) symptom recurrence after 6 months of follow-up. However, she experienced chronic kidney disease stage G3b. Histological analysis did not show any villous atrophy or intraepithelial lymphocyte infiltrates within the duodenum or the colon biopsy. Discussion and conclusion: This case highlights the broad spectrum of clinical manifestations and histological findings in Olmesartan-induced enteropathy. It also highlights the importance of rapid diagnosis in order to limit organ damage such as chronic kidney disease. Full article