Background: Ubiquitination is a reversible process of posttranslational protein modification through the action of the family of deubiquitylating enzymes which contain ubiquitin-specific protease 9x (USP9X). Recent evidence indicates that USP9X is involved in the progression of various human cancers. The aim was to detect the expression of USP9X in the progression from normal epithelium to invasive esophageal squamous cell cancer (ESCC) and evaluate the relevance of USP9X expression to the tumor progression and prognosis.Methods: In this study, USP9X immunohistochemical analysis was performed on tissues constructed from ESCC combined with either normal epithelium or adjacent precursor tissues of 102 patients. All analyses were performed by SPSS 13.0 software.Results: We observed that the level of high USP9X expression increased gradually in the transformation from normal epithelium (4.0%), to low grade intraepithelial neoplasia (10.5%), then to high grade intraepithelial neoplasia (28.6%), and finally to invasive ESCC (40.2%). The expression of USP9X was found to be significantly different between the normal mucosa and ESCC (P < 0.001), and between low grade intraepithelial neoplasia and high grade intraepithelial neoplasia (p = 0.012). However, no difference was observed between the high expression of USP9X in normal mucosa and low grade intraepithelial neoplasia (P = 0.369), nor between high grade intraepithelial neoplasia and ESCC (p = 0.115). Interestingly, the most intensive staining for USP9X was usually observed in the basal and lower spinous layers of the esophageal epithelium with precursor lesions which often resulted in the earliest malignant lesion. USP9X expression status was positively associated with both depth of invasion (p = 0.046) and lymph node metastasis (p = 0.032). Increased USP9X expression was significantly correlated to poorer survival rate in ESCC patients (p = 0.001). When adjusted by multivariate analysis, USP9X expression (HR 2.066, P = 0.005), together with TNM stage (HR 1.702, P = 0.042) was an independent predictor for overall survival.Conclusions: Up-regulation of USP9X plays an important role in formation and progression of precancerous lesions in ESCC and USP9X expression levels were significantly correlated with the survival of ESCC patients. Thus, USP9X could be considered as a potential biomarker and prognostic predictor for ESCC.Virtual slides: The virtual slides for this article can be found here:http://www.diagnosticpathology.diagnomx.eu/vs/1945302932102737

Background: As an acute-phase protein, serum amyloid A (SAA) is expressed primarily in the liver. However, its expression in extrahepatic tissues, especially in tumor tissues, was also demonstrated recently. In our study, we investigated the expression of SAA in uterine cervical carcinomas, and our results suggested its potential as a serum biomarker.Methods: Quantitative real-time polymerase chain reaction (RT-PCR), immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA) were used to evaluate the SAA gene and protein expression levels in the tissues and sera of patients with non-neoplastic lesions (NNLs), cervical intraepithelial neoplasia (CIN) and cervical carcinoma (CC).Results: Compared with NNLs, the SAA gene (SAA1andSAA4) expression levels were significantly higher in uterine CC (mean copy numbers: 138.7 vs. 5.01, P < 0.000; and 1.8 vs. 0.079, P = 0.001, respectively) by real-time PCR. IHC revealed cytoplasmic SAA protein staining in tissues from adenocarcinoma and squamous cell carcinoma of the cervix. The median serum concentrations (μg/ml) of SAA were 6.02 in patients with NNLs and 10.98 in patients with CIN (P = 0.31). In contrast, the median serum SAA concentration was 23.7 μg/ml in uterine CC patients, which was significantly higher than the SAA concentrations of the NNL group (P = 0.002) and the CIN group (P = 0.024).Conclusions: Our data suggested that SAA might be a uterine CC cell product. High SAA concentrations in the serum of CC patients may have a role in monitoring disease occurrence and could have therapeutic applications.Virtual slides: The virtual slide(s) for this article can be found here:http://www.diagnosticpathology.diagnomx.eu/vs/1433263219102962

Exosomes derived from bone marrow‐derived mesenchymal stem cells (BMSCs) can alleviate the symptoms of pelvic floor dysfunction (PFD) in rats. However, the potential therapeutical effects of exosomes derived from BMSCs treated with tumour necrosis factor (TNF)‐α on the symptoms of PFD in rats are unknown. Exosomes extracted from BMSCs treated with or without TNF‐α were applied to treat PFD rats. Our findings revealed a significant elevation in interleukin (IL)‐6 and TNF‐α, and matrix metalloproteinase‐2 (MMP2) levels in the vaginal wall tissues of patients with pelvic organ prolapse (POP) compared with the control group. Daily administration of exosomes derived from BMSCs, treated either with or without TNF‐α (referred to as Exo and TNF‐Exo), resulted in increased void volume and bladder void pressure, along with reduced peak bladder pressure and leak point pressure in PFD rats. Notably, TNF‐Exo treatment demonstrated superior efficacy in restoring void volume, bladder void pressure and the mentioned parameters compared with Exo treatment. Importantly, TNF‐Exo exhibited greater potency than Exo in restoring the levels of multiple proteins (Elastin, Collagen I, Collagen III, IL‐6, TNF‐α and MMP2) in the anterior vaginal walls of PFD rats. The application of exosomes derived from TNF‐α‐treated BMSCs holds promise as a novel therapeutic approach for treating PFD.

This study aimed to elucidate the roles of junctional adhesion molecule 2 (JAM‐2), collagen I and matrix metalloproteinase 2 (MMP‐2) in the pathogenesis of pelvic organ prolapse (POP) and explore their potential as diagnostic markers. We examined 82 POP patients and 64 controls using enzyme‐linked immunosorbent assay (ELISA) and quantitative Polymerase Chain Reaction (qPCR) to analyse protein and gene expression levels of JAM‐2, Collagen I and MMP‐2. Receiver operating characteristic (ROC) analysis evaluated their diagnostic efficacy, with correlation analyses linking molecular markers to POP severity based on POP‐Q grades. Our study found no significant differences in age, BMI and vaginal parity between POP patients and controls. Molecular analyses revealed significant alterations in the expression levels of JAM‐2, Collagen I and MMP‐2 in POP patients. Specifically, there was a marked decrease in JAM‐2 and collagen I levels, accompanied by an increase in MMP‐2 expression, indicating a disruption in the balance between tissue synthesis and degradation. ROC analysis demonstrated the significant discriminative power of these markers, with substantial area under the curve (AUC) values for diagnosing POP. Correlation analysis further showed a significant association between the expression of JAM‐2, Collagen I and MMP‐2 and the clinical severity of POP, as indicated by POP‐Q grades. Our findings revealed the significant changes in the expression of JAM‐2, Collagen I and MMP‐2 that may contribute to the POP pathogenesis. The diagnostic potential of these markers was substantiated, suggesting their utility in developing noninvasive diagnostic tools for POP.

To develop a simple preoperative risk score identifying women requiring invasive hemostatic interventions during cesarean delivery. This retrospective coho

Background: Early-onset preeclampsia (EOPE) is a severe hypertensive disorder of pregnancy associated with preterm delivery and maternal multi-organ dysfunction. Although placental senescence and immune dysregulation have been implicated in EOPE, the expression profile of senescence-related genes(SRGs) and their mechanistic roles in disease progression remain unclear. Methods: Multiple placental bulk RNA-seq datasets were integrated to identify senescence-related differentially expressed genes in EOPE. Weighted gene co-expression network analysis (WGCNA) and multiple machine learning algorithms were used to identify hub genes. Single-cell RNA sequencing was further applied to define the cellular expression patterns of hub genes and characterize senescence-associated changes in EOPE. Key findings were subsequently validated in clinical placental specimens using molecular and functional experiments. Results: A total of 44 senescence-related differentially expressed genes were identified in EOPE placentas and were mainly enriched in cell proliferation-related pathways. LEP, ENG, MIF, and CYBB were identified as hub genes and were predominantly expressed in trophoblasts and immune cells. Single-cell analysis showed that senescence-associated activity was primarily enriched in the trophoblast lineage and further implicated LEP in syncytiotrophoblast (SCT) senescence and SCT secretory dysfunction, suggesting a role in EOPE pathogenesis. Conclusions: Our findings suggest that EOPE is closely related to placental senescence. Deeper investigation of SRGs and pathways may aid early diagnosis and clarify the molecular basis of EOPE.