Identification and validation of ferroptosis-related prognostic gene signature in patients with cervical cancer.

Background: Ferroptosis is an iron-dependent cell death, which is distinct from the other types of regulated cell death. Considerable studies have demonstrated that ferroptosis is involved in the biological process of various cancers. However, the role of ferroptosis in cervical cancer (CC) remains unclear. This study aims to explore the ferroptosis-related prognostic genes (FRPGs) expression profiles and their prognostic values in CC. Methods: The ferroptosis-related genes (FRGs) were obtained from The Cancer Genome Atlas (TCGA) and FerrDb databases. Core FRGs were determined by the Search Tool for the Retrieval of Interacting Genes (STRING) website. FRPGs were identified using univariate and multivariate Cox regressions, and the ferroptosis-related prognostic model was constructed. FRPGs were verified in clinical specimens. The relationship between FRPGs and tumor infiltrating immune cells were assessed through the CIBERSORT algorithm and the LM22 signature matrix. Bioinformatics functions of FRPGs were explored with the Database for Annotation, Visualization, and Integrated Discovery (DAVID). Results: Thirty-three significantly up-regulated and 28 down-regulated FRGs were screened from databases [P<0.05; false discovery rate (FDR) <0.05; and |log2 fold change (FC)| ≥2]. Twenty-four genes were found closely interacting with each other and regarded as hub genes (degree ≥3). Solute carrier family 2 member 1 (SLC2A1), carbonic anhydrases IX (CA9), and dual oxidase 1 (DUOX1) were identified as independent prognostic signatures for overall survival (OS) in a Cox regression. Time-dependent receiver operating characteristic (ROC) curves showed the predictive ability of the ferroptosis-related prognostic model, especially for 1-year OS [area under the curve (AUC) =0.76]. Consistent with the public data, our experiments demonstrated that the mRNA levels of SLC2A1 and DUOX1, and the protein levels of SLC2A1, DUOX1, and CA9 were significantly higher in the tumor tissues. Further analysis showed that there was a significant difference in the proportion of tumor infiltrating immune cells between the low- and high-risk group based on our prognostic model. The function enrichment of FRPGs was explored by applying Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Conclusions: In this study, the features of FRPGs in CC were pictured. The results implicated that targeting ferroptosis may be a new reliable biomarker and an alternative therapy for CC.

Non-Lactobacillus-Dominated Vaginal Microbiota Is Associated With a Tubal Pregnancy in Symptomatic Chinese Women in the Early Stage of Pregnancy: A Nested Case-Control Study.

The features of the vaginal microbiota (VM) community can reflect health status, and they could become new biomarkers for disease diagnosis. During pregnancy, domination of bacteria of the genus Lactobacillus in the VM community is regarded as a keystone because they stabilize the VM by producing antimicrobial compounds and competing adhesion. An altered VM composition provides a marker for adverse pregnancy outcomes. This nested case-control study aimed to characterize the VM in women with a tubal pregnancy (TP) presenting with pain and/or uterine bleeding in early pregnancy. Chinese women with a symptomatic early pregnancy of unknown location were the study cohort. 16S rDNA gene-sequencing of V3-V4 variable regions was done to assess the diversity, structures, taxonomic biomarkers, and classification of the VM community. The primary outcome was the location of the early pregnancy. The VM community in women with a TP showed higher diversity (PD-whole-tree, median: 8.26 vs. 7.08, P = 0.047; Shannon Diversity Index, median: 1.43 vs 0.99, P = 0.03) and showed different structures to those in women with an intrauterine pregnancy (IUP) (R = 0.23, P < 0.01). Bacteria of the genus Lactobacillus were significantly enriched in the IUP group, whereas bacteria of the genera Gardnerella and Prevotella were significantly enriched in the TP group. Lactobacillus abundance could be used to classify the pregnancy location (AUC = 0.81). Non-Lactobacillus-dominated microbiota (≤ 0.85% Lactobacillus) was significantly associated with a TP (adjusted odds ratio: 4.42, 95% confidence interval: 1.33 to 14.71, P = 0.02). In conclusion, among women with a symptomatic early pregnancy, a higher diversity and lower abundance of Lactobacillus in the VM is associated with a TP.

[Inhibitory effect of telomerase inhibitors combined with X-irradiation on bone marrow hematopoiesis in mice].

The purpose of this study was to evaluate the effect of telomerase inhibitors combined with X-irradiation on bone marrow hematopoiesis in tumor-carrying mice. With an orthogonal experiment design, the telomerase inhibitors [azidothymidine, AZT 300 mg/(kg.day) and lamivudine 150 mg/(kg x day), per os, bid, x 2 weeks] and X-irradiation [total dose 10 Gy (2 Gy x 5) in 1 week] were used to treat BALB/c mice carrying breast cancer MA(782) for evaluating the influence on peripheral blood cells, bone marrow nucleated cells and telomerase activity. Telomerase activity was detected by a PCR-based telomeric repeat amplification protocol (TRAP) coupled with ELISA. The results showed that the number of marrow nucleated cells (x 10(7)/femur) was 2.1875 in untreated group, and 1.7375, 1.7500 and 1.3475 in irradiated, lamivudine and AZT groups, respectively, these suggested that AZT and irradiation could obviously decrease the number of marrow nucleated cells (P< 0.01 or P < 0.05). The peripheral WBC increased 3.7% in untreated mice, and irradiation, lamivudine and AZT reduced 18.09%, 16.19% and 41.00% of WBC, respectively (P < 0.05). Irradiation, lamivudine and AZT showed no obvious effect on RBC and platelet counts (P > 0.05). The telomerase activity (A(450) nm) of marrow cells was 1.498, 1.483, 0.816 and 0.727 in untreated, irradiation, lamivudine and AZT groups, respectively. It is concluded that AZT and lamivudine combined with X-irradiation inhibit bone marrow nucleate cells and the peripheral WBC, manifest inhibitory effect on telomerase activity in murine bone marrow, but have no effect on the peripheral RBC and platelet.