Characterization of pyroptosis-related genes in esophageal cancer and construction of a prognostic model.

OBJECTIVE: Esophageal cancer (EC) is a highly malignant digestive system tumor that often lacks evident early symptoms and has a poor prognosis. Pyroptosis, a form of programmed cell death, has been shown to be associated with the occurrence and progression of many malignancies. However, its role in esophageal cancer remains unclear. This work aimed to evaluate the prognostic value of pyroptosis-related genes (PRGs) in EC using data from The Cancer Genome Atlas (TCGA) cohort. MATERIALS AND METHODS: The RNA-seq data from 171 esophageal samples in the TCGA database were employed. Differential expression genes (DEGs) between tumor and non-tumor samples were compared. Protein-protein interaction (PPI) networks were constructed using the STRING database, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and Gene Ontology (GO) analyses were performed using the "clusterProfiler" package in R. Furthermore, based on the DEGs, all esophageal cancer cases were classified into three subtypes. A risk model for gene features was established using the LASSO regression method, and EC patients in the TCGA cohort were divided into high-risk and low-risk groups. RESULTS: A total of 614 PRGs were identified. Among them, 32 DEGs (31 upregulated and 1 downregulated) were found between normal esophageal tissue and EC tissue. PPI analysis identified key genes including IL-1ß, CASP1, AIM2, HMGB1, GSDMD, PYCARD, IL-18, BAK1, and TP53. On the other hand, the low-risk group exhibited a significantly higher survival rate than the high-risk group (p < 0.001). Combined with the clinical characteristics of the TCGA cohort, it was found that the risk score was an independent prognostic factor for overall survival (OS) prediction in EC patients. KEGG and GO analyses revealed the enrichment of genes associated with cell proliferation in the high-risk group. CONCLUSIONS: PRGs play a crucial role in the occurrence and development of EC and can be used to predict the prognosis of EC patients.

High expression of WISP1 promotes metastasis and predicts poor prognosis in hepatocellular carcinoma.

OBJECTIVE: The aim of this study was to explore the expression level of Wnt1-inducible signaling pathway protein 1 (WISP1) and its clinical significance in hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was performed to detect the expression level of WISP1 in HCC tissues and cells. Kaplan-Meier curves and Cox proportional hazard regression model were chosen for single and multiple factor analysis of survival analysis, respectively. Furthermore, wound healing assay and transwell assay were used to verify the effect of WISP1 on HCC cell metastasis in vitro. RESULTS: The expression level of WISP1 in HCC tissues was significantly higher than that in para-cancer tissues (p<0.05). WISP1 expression was positively correlated with lymph node metastasis and clinical stage of HCC. Kaplan-Meier curve showed that HCC patients with higher WISP1 expression exhibited significantly worse progression free survival (PFS) time and overall survival (OS) time. Both univariate and multivariate analysis indicated that high expression of WISP1 was an independent predictor of poor prognosis in HCC. In addition, WISP1 significantly promoted the invasion and migration of HCC cells in vitro. CONCLUSIONS: WISP1 might contribute to the development of HCC, serving as a clinical biomarker and therapeutic target for HCC patients.

Altered expression of survivin, Fas and FasL contributed to cervical cancer development and metastasis.

OBJECTIVE: To evaluate the expression of apoptosis-related genes and their correlation with prognosis in cervical cancer patients. MATERIALS AND METHODS: The expressions of Survivin, Fas and FasL in tissues of cervical cancer, cervical intraepithelial neoplasia (CIN), chronic cervicitis and normal cervix wer detected by immunohistochemical staining, and the relationship between the expression of Survivin, Fas and FasL and clinical pathologic characteristics of cervical cancer was correlation analysis. RESULTS: The positive expression rates of Survivin and FasL in cervical cancer tissues were significantly higher than those in tissues of normal cervix, chronic cervicitis and CIN (p < 0.05), but lower positive expression rate of Fas was observed in cervical cancer tissues when compared with that in normal cervix, chronic cervicitis and CIN tissues (p < 0.05). The expression of Survivin was significantly correlated with clinical staging and lymph node metastases of cervical cancer (p < 0.05). The expression of FasL was correlated with lymph node metastases, clinical staging and pathological grading of cervical cancer (p < 0.05). The expression of Survivin was negatively correlated with that of Fas (r = -0.517, p < 0.01), but positively correlated with that of FasL (r = 0.381, p < 0.01) in tissues of cervical cancer. CONCLUSIONS: The up-regulated expression of Survivin and FasL and down-regulated expression of Fas may be involved in the carcinogenesis and development of cervical cancer. The expression of FasL may be one of the prediction indexes for disease progression and prognosis in cervical cancer.

A novel CB receptor GPR55 and its ligands are involved in regulation of gut movement in rodents.

BACKGROUND: This study was to investigate the effects of the novel cannabinoid receptor - G protein-coupled receptor 55 (GPR55) - and its ligands O-1602 and cannabidiol (CBD) on gastrointestinal (GI) motility in rodents. METHODS: Lipopolysaccharide (LPS) was used in vivo to produce the model of septic ileus. The intestinal motility was measured by recording myoelectrical activity of jejunum in rats, and by measuring GI transit with a charcoal marker in mice, in presence of O-1602 or CBD. Inflammatory response was assessed serologically and histologically. The expression and distribution of GPR55 in the different parts of rat intestine were investigated by real-time PCR and immunohistochemistry. In vitro, the effects of the drugs on the GI movement were investigated by measuring the contraction of the intestinal muscle strips in organ bath, and the intracellular responses of the muscle cells with microelectrode technique. KEY RESULTS: G protein-coupled receptor 55 was expressed in different parts of rat intestine. Lipopolysaccharide significantly inhibited the intestinal motility, increased inflammatory cytokines and GPR55 expression. Pretreatment with CBD normalized LPS-induced hypomotility and improved the inflammatory responses serologically and histologically. Both O-1602 and CBD counteracted LPS-induced disturbances of the gut contraction, but had no effect on the membrane potential of the muscle cells, while cannabinoid type 1 receptor antagonist AM251 and cannabinoid type 2 receptor antagonist AM630 increased the potential. CONCLUSIONS & INFERENCES: G protein-coupled receptor 55 existed throughout the whole intestine of rats. O-1602 or CBD selectively normalized the motility disturbances. Possible mechanisms involved systemic anti-inflammation and the regulation of myoelectrical activity of the intestine.

Plasticity of ovarian cancer cell SKOV3ip and vasculogenic mimicry in vivo.

The aim of this study is to investigate the plasticity of human epithelial ovarian cancer cell SKOV3ip and formation of vasculogenic mimicry (VM) in vivo. SKOV3ip was transfected with lentiviral vector carrying green fluorescence protein (GFP). Female nude mice were implanted intraperitoneally with GFP-labled SKOV3ip. When the transplanted tumor reached a volume of approximately 1 cm(3), paraffin-embedded, formaldehyde-fixed tissue was prepared and stained with hematoxylin and eosin (H & E). Tumor tissues were also studied by electron microscopy and fluorescence microscopy. The results of H & E staining, electron microscopy, and fluorescence microscopy indicated SKOV3ip formed patterned networks with erythrocytes in them, in the absence of vascular epithelial cells, which was a sign that SKOV3ip engaged in VM in vivo. Expression of vascular epithelium marker CD31 was investigated by immunohistochemical staining, immunofluorescence assay, semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR), and flow cytometric analysis (FACS). Factor VIII and vascular endothelial growth factor (VEGF) were also analyzed by FACS. Weak and focal CD31 immunohistochemical staining was found along the channels of tumor cells. Immunofluorescence assay and RT-PCR demonstrated that CD31 was expressed in primary-cultured SKOV3ip. CD31 and Factor VIII, but not VEGF were detected in primary-cultured SKOV3ip by FACS. The present study has shown that human ovarian cancer cell line SKOV3ip may be able to express some specific markers of vascular epithelial cells and has plasticity to form VM in vivo. In the following study, we indicated that hypoxia-inducible factor (HIF)-1alpha inhibitor, rapamycin, could possibly prevent VM and phenotype transformation of SKOV3ip, reflected by down-regulating expression of CD31 and Factor VIII. HIF-1alpha protein expression correlated with CD31 and Factor VIII protein expression in SKOV3ip. These results indicated that VM might be associated with HIF-1alpha.

A clinically relevant orthotopic implantation nude mouse model of human epithelial ovarian cancer--based on consecutive observation.

The aim of this study is to establish an orthotopic implantation nude mouse model of epithelial ovarian cancer (EOC) and observe its biologic features. A human ovarian tumor line SKOV3ipl previously grown subcutaneously was implanted orthotopically as intact tissue into the ovarian capsule of 64 nude mice. Every week eight mice were taken randomly, and the tumor growth pattern and extent of metastatic disease were monitored continuously. Those mice that died of disease were necropsied and the end date was recorded. The orthotopic implanted tumors demonstrated a 100% take rate. Three weeks after implantation the tumors grew fast and weighed 1149 +/- 152 mg, and 5 weeks after implantation the tumors reached a flat stage. The tumors metastasized more often to peritoneum (32/56) and diaphragm (18/56), then to pelvic lymph nodes (11/56) and lung (10/56), and then to the seldom invaded organs including the pancreas, the liver, the contralateral ovary, and the para-aortic lymph node. Eight nude mice became exhausted 7 weeks after implantation and died within 68 days after implantation. Our study, utilizing the SKOV3ipl cell, is the first model of consecutive observation of the process of invasion and metastasis of EOC. It should be useful in understanding the molecular biology of EOC and in the development of therapeutic modalities against metastasis.

Optical properties of an ionic-type phononic crystal

An ionic-type phononic crystal composed of two ferroelectric media with opposite spontaneous polarization aligned periodically in a superlattice structure was studied theoretically and experimentally. The coupling between vibrations of the superlattice and the electromagnetic waves results in various long-wavelength optical properties, such as microwave absorption, dielectric abnormality, and polariton excitation, that exist originally in ionic crystals. The results show that this artificial crystal structure can be used to simulate the microscopic physical processes in real crystals.