This study evaluated the therapeutic effect of hesperidin (HES) on allergic rhinitis (AR) in a mouse model induced by ovalbumin (OVA). After inducing AR in BALB/c mice through OVA, the severity of allergic reactions was assessed through behavioral scoring. The levels of OVA-specific IgE, histamine, and IL-6 were measured by ELISA. Pathological changes, mast cell infiltration, and protein expression, were detected using ELISA, histopathological staining, immunohistochemistry (IHC), and Western blot. The human nasal epithelial cells (RPMI-2650) were used and the epithelial barrier function was evaluated through transepithelial resistance (TEER) and FITC-dextran permeability assays. The results indicated that after HES intervention, the frequency of nasal rubbing and sneezing in mice significantly decreased, and the levels of serum OVA-specific IgE, histamine, and IL-6 also significantly reduced. Additionally, HES could alleviate nasal mucosal epithelial damage and inflammatory cell infiltration, while reducing mast cell aggregation. HES also inhibited the expression of p-p65 and p-IκBα, while enhancing the protein expression of ZO-1 and Occludin. In vitro experiments showed that HES could reverse the decrease in TEER, increase in FITC-dextran permeability, and decrease in ZO-1 and Occludin expression induced by OVA in HNEpC cells. However, when the NF-κB pathway was activated by TNF-α, the protective effect of HES was significantly diminished. In conclusion, HES could alleviate OVA-induced AR symptoms in mice by inhibiting the activation of the NF-κB signaling pathway, reducing inflammatory responses, and restoring the expression of tight junction proteins in the nasal epithelium.
The lack of lineage-specific markers and overlapping shape make undifferentiated round cell cancers of the oral cavity extremely difficult to diagnose. We describe a 47-year-old female patient who had a submucosal lesion affecting her mandibular gingiva and labial mucosa. Histopathological analysis showed that the stroma was infiltrated by sheets of monotonous round cells with hardly noticeable nucleoli without any epithelial involvement. The results of a comprehensive immunohistochemistry panel that included cytokeratin, CD45, S100, desmin, synaptophysin, CD99, CD117, MyoD1, CK20, TTF-1, ER, PR, and INI1 were negative, ruling out metastatic disease and epithelial, lymphoid, melanocytic, myogenic, and neuroendocrine differentiation. Certain poorly differentiated carcinomas were further ruled out by retained INI1 expression and negative NUT. A diagnosis of undifferentiated round cell sarcoma, not otherwise described, was made in the absence of an identifiable primary tumor and conclusive immunophenotype. This case thereby emphasizes the value of a methodical exclusion-based strategy and the necessity of supplementary molecular tests in the diagnosis of head and neck tumors that are difficult to diagnose.
Clear cell renal cell carcinoma (ccRCC) carries a high risk of recurrence, necessitating reliable prognostic biomarkers. This study evaluated the immunohistochemical expression, clinicopathological significance, and prognostic value of Musashi-1 (MSI1) and MTFR2 in ccRCC. Expression of MSI1 and MTFR2 was evaluated by immunohistochemistry in 124 ccRCC cases and paired non-neoplastic renal tissues. Associations with clinicopathological parameters and prognostic scoring models (SSIGN, UISS, SIS) were assessed, applying False Discovery Rate (FDR) procedures for multiple hypothesis testing. Progression-free survival (PFS) and disease-free survival (DFS) were analyzed using Kaplan–Meier curves, log-rank tests, and multivariate Cox regression models with multicollinearity diagnostics (VIF). Both MSI1 and MTFR2 were significantly upregulated in ccRCC compared to normal tissues (p < 0.001) and positively correlated with each other (r = 0.676, p < 0.001). High expression of either marker was significantly associated with adverse baseline features (larger tumour size, higher WHO/ISUP grade, advanced T-stage; q < 0.05) and higher-risk SSIGN, UISS, and SIS scores. Elevated MSI1 and MTFR2 predicted significantly shorter PFS and DFS (p < 0.001). Multivariate analysis confirmed T-stage, WHO/ISUP grade, MSI1, and MTFR2 as independent prognostic factors for PFS and DFS. The MSI1/MTFR2 axis represents strong independent prognostic signature in ccRCC and may enhance risk stratification while highlighting potential therapeutic targets.
The pathogenesis of cancer is characterized by the acceleration of tumor growth, inhibition of tumor suppression, genetic and epigenetic alteration, lubricative transformation and tumor microenvironment. Extramammary Paget’s disease (EMPD) is a rare skin cancer that originates from apocrine glands in genital and axillary area. Although the pathogenesis of EMPD is still poorly understood, increasing evidence reveals that the mechanism of EMPD progression is regulated by the acquired ability of EMPD cells and tumor microenvironment. HER2/PI3K/AKT signaling and hormone receptor pathways are activated. Whereas tumor mutation burden is low, numerous driver genes such as ERBB2 and PIK3CA are detected. Tumor evolution in EMPD is characterized by high genetic intratumor heterogeneity with shared background factors. Tumor microenvironment in EMPD promotes immune evasion through the reduction of reduced CD4 + and CD8 + T cells and the increase of Treg cells and CD163 + macrophages. Enhanced Warburg effect and S. aureus contribute to the suppression of antitumor immunity. This review focuses on the mechanism of malignant progression in EMPD (hallmarks of EMPD).
Primary biliary cholangitis (PBC) is an autoimmune-related cholestatic liver disease predominantly affecting women, yet sex-specific differences in progression remain unclear. Multicenter retrospective analysis of 289 Japanese PBC patients compared sex disparities in demographics, laboratory parameters, histopathology, and prognostic scores. Males tended to be older at diagnosis, although this difference did not reach statistical significance. At diagnosis, significant laboratory differences were observed in total bilirubin and γGT, both higher in males (p < 0.05), consistent with a slightly higher ALBI score in males (p = 0.046), suggesting worse liver functional reserve. Males also had worse outcomes according to UK‑PBC Risk Scores and GLOBE score (p < 0.05). Histologically, at comparable bile duct loss, males tended to exhibit higher orcein‑positive granule deposition scores than females, suggesting chronic cholestasis resulting from bile duct loss tends to be more pronounced in males. Furthermore, positive correlations between fibrosis and bile duct loss, and between fibrosis and orcein‑positive granule deposition, were observed in females but not in males. Among mild‑fibrosis patients, males exhibited greater orcein-positive granule deposition. This study demonstrates sex differences in PBC progression and suggests that males may exhibit more pronounced chronic cholestatic changes, as reflected by greater orcein‑positive granule deposition, particularly in mild fibrosis.
