Mechanism of Human Tubal Ectopic Pregnancy Caused by Cigarette Smoking.

In the past few decades, the smoking rate of women of childbearing age has increased. Epidemiological data has repeatedly shown that smoking women have an increased risk of various reproductive diseases, including ectopic pregnancy (EP), decreased fertility, adverse pregnancy outcomes, and failure of assisted reproduction. The oviduct was the target of cigarette smoke in many in vivo and in vitro studies. The fallopian tube is a well-designed organ. Its function is to collect and transport the ova to the fertilized site and provide a suitable environment for fertilization and early embryonic development. Lastly, the fallopian tube transports the pre-implantation embryo to the uterus. Various biological processes can be studied in the fallopian tubes, making it an excellent model for toxicology. This paper reviews the roles of the fallopian tube in gametes and embryo transportation, and the possible mechanism tobacco smoke contributes to tubal EP. A possible signal pathway might be a model to develop intervention of EP for pregnant women exposed to smoking.

Novel Hub genes co-expression network mediates dysfunction in a model of polycystic ovary syndrome.

BACKGROUND: This study aimed to integrate DNA methylation, miRNA, and mRNA microarray data to construct a gene co-expression network for polycystic ovarian syndrome (PCOS). METHODS: The weighted gene co-expression network analysis (WGCNA) was conducted to construct a PCOS-related co-expression network by using the GEO public datasets. We performed Gene Ontology and KEGG pathway enrichment analyses for a further exploration of gene function in networks. Finally, the dysfunction module consisting of a co-expression network was mapped to the PCOS patients and tried to provide guidance to the PCOS phenotyping. RESULTS: Three modules (Midnightbule, Pink, and Red) were identified to be PCOS-related by WGCNA analysis. These module-related genes were enriched in cell response to stimulus, PI3K-Akt signaling pathway, insulin biological process, signaling pathway, and cytokine-cytokine receptor interaction biological processes. The multiple-factor network, including miRNA-lncRNA and DNA methylation-mRNA interaction, was closely associated with PCOS dysfunction. CONCLUSION: Our study render a novel insight into the mechanisms and might provide candidate biomarkers and therapeutic targets for the classification of PCOS dysfunction.

Tubal ectopic pregnancy occurrence is associated with high expressions of prokineticin receptors and aberrant secretion of inflammatory cytokines.

OBJECTIVE: Tubal ectopic pregnancy (TEP) remains the most common cause of maternal morbidity and mortality in the early months of pregnancy. The aim of this study is to perform the correlation between PROKRs and pro-inflammatory genes and explore the role of novel genes in pathogenesis of TEP. METHODS: Here, quantitative real time PCR and immunohistochemistry were used to assess the expression of the novel genes in 120 TEP patients and 30 age-matched non-TEP patients. The correlation between PROKRs and pro-inflammatory genes were analyzed by Pearson correlation coefficient. Univariate and multivariate Cox regression analyses were used to assess the risk prediction rate of novel genes. Receiver operating characteristic was used to assess the performance of our model. RESULTS: PROKRs (PROKR1 and PROKR2) and pro-inflammatory genes (TNF-α, IL-6, and IL-8) expression levels significantly enhanced in TEP patients, and significantly positive correlation with pro-inflammatory genes for PROKRs. A multivariate Cox regression analysis demonstrated that 2 genes (PROKR2 and IL8) had significant diagnostic value, which were associated with the occurrence and development of TEP. CONCLUSION: Our data further denote that dysregulation of PROKR2 and IL-8 were risk factor and played an important role in the pathogenesis of TEP.

Prognostic Factors among Brain Metastases in Newly Diagnosed Ovary Cancer: A Large Real-world Study.

Background: Population-based data on the prognosis of brain metastases at initial diagnosis of ovary cancer (OCBM) are currently lacking. Besides, the effective treatment for OCBM patients is still controversial now. The study aimed to explore the prognostic factors among OCBM. Methods: We retrospectively reviewed the OCBM patients from the Surveillance, Epidemiology, and End Result (SEER) database of the National Cancer Institute to investigate predictors of the presence of OCBM and its' prognostic factors related to all-cause mortality. We employed multivariable logistic and Cox regression analysis. Furthermore, to minimize the impact of potential confounding factors, we conducted a 1:1 propensity score matching (PSM) analysis. Results: A total of 29,512 cases of OC patients entered into the study, including 89 patients with brain metastases of ovarian cancer, which accounted for 0.30% of the entire cohort and 12.02% of the metastatic disease subset. We identified eight factors, including laterality, histology, surgery, radiotherapy, chemotherapy, and extracranial metastatic sites to bone, liver, and lung, as predictors of OCBM based on multivariable logistic regression among the entire cohort. The median survival time of OCBM was 2.0 months, and the interquartile range was 2.0-10.0 mo. The patients who received comprehensive treatment had better prognosis. Based on the multivariable Cox model, marital status, surgery, chemotherapy, and extensive therapy (including RSC, SC, and RC) were identified as predictors of OS. Besides, a new factor (brain metastasis) was identified by 1:1 PSM -based multiple Cox regression, apart from the above prognostic factors for OS. Conclusions: This study provided a population-based estimate of the proportion and prognosis for newly diagnosed ovary cancer with brain metastases. These findings may add materials to guidelines for preliminary screening and optimal treatment of OCBM patients.

MicroRNA-142-3p suppresses endometriosis by regulating KLF9-mediated autophagy in vitro and in vivo.

The detailed pathogenesis of endometriosis remains largely unclear despite decades of research. Recent studies have demonstrated that miRNAs plays an important role in endometriosis. The expression of miR-142-3p was decreased in ectopic endometrial tissues, while KLF9 and VEGFA expression levels were increased. Overexpression of miR-142-3p or knockdown of KLF9 significantly suppressed CRL-7566 cell proliferation and metastasis, induced cell apoptosis, and decreased both cell autophagy and vascularization. Additionally, KLF9 was confirmed to be a direct target of miR-142-3p and to directly bind to the promoter of the VEGFA gene, regulating its expression. Finally, intraperitoneal injection of miR-142-3p lentivirus significantly attenuated ectopic endometriotic lesions in vivo.miR-142-3p directly targeted KLF9, regulated VEGFA expression, and was protective against the growth of ectopic endometriotic lesions. Therefore, the miR-142-3p/KLF9/VEGFA signalling pathway may be a potential target in endometriosis treatment.

[Progress of research on protein composition and gene therapy of Fanconi anaemia - review].

Fanconi anaemia (FA) is an autosomal recessive inherited disorder caused by defects in hematopoietic stem cells. The clinical manifestations of FA are diverse and complicated. FA cells display high hypersensitivity to agents which produce interstrand DNA cross-links such as mitomycin C (MMC) or diepoxybutane (DEB). At least eight complementation groups with defects in eight genes (FANCA, FANCB, FANCC, FANCD(1), FANCD(2), FANCE, FANCF and FANCG) have been identified by gene analysis. Six genes (corresponding to subtypes A, C, D(2), E, F and G) have been coloned, and the encoded FA proteins interact in a common cellular pathway - "FA Pathway", through which modulate DNA repair. The progress of research on FA molecular mechanism provides gene therapy of FA with theory basis. FA cells transduced with the use of retrovirus carring the normal FA gene cDNA manifestate phenotypic correction of hypersensitivity to DNA cross-linking agents, such as MMC. In this review the clinical manifestations and gene composition of FA, and the functions of encoded FA proteins were summarized. The hematopoietic stem cell transplantation and gene therapy for FA patients were discussed.