Project description:This study focuses on the potential of detecting endometrial cancer based on the proteins and peptides expressed in cervico-vaginal fluid.Sequential window acquisition of all theoretical mass spectra (SWATH-MS), an accurate and reproducible platform for analysing biological samples, offers a technological advance for biomarker discovery due to its reproducibility, sensitivity and potential for data re-interrogation. SWATH-MS requires a spectral library in order to identify and quantify peptides from multiplexed mass spectrometry data.Here, we present a spectral library of thousands of proteins in the cervico-vaginal fluid of women with or at risk of endometrial cancer. Pooled cervico-vaginal fluid samples from 19 women, comprising of 9 endometial cancer cases(both endometriod and non-endometriod), 3 atypical hyperplasias and 7 controls (symptomatic post-menopausal women with no evidence of endometrial cancer) were used for library generation. We have combined these data with a library of over 6,000 proteins generated based on mass spectrometric analysis of two endometrial cancer cell lines This important resource will enable the identification of endometrial cancer biomarkers in cervico-vaginal fluid and advances our knowledge of the role of proteomics in endometrial cancer detection.
Project description:The aim of the underlying study was to identify protein signatures for the detection of endometrial cancer in minimally invasive samples such as cervico-vaginal fluid and blood plasma. Plasma and Delphi Screener-collected cervico-vaginal fluid samples were acquired from post-menopausal women who were symptomatic with (n=53)and without(n=65)endometrial cancer. Digitised proteomic maps were developed for each sample by sequential window acquisition of all theoretical mass spectra (SWATH-MS). Machine learning was employed to identify the most discriminatory proteins and a set of high-perfoming biomarker signatures obtained.
Project description:Griffithsin (GRFT) is an anti-viral lectin with potent anti-HIV activity. GRFT’s preclinical safety, lack of systemic absorption after topical administration, and lack of cross-resistance with existing products prompted its development for topical HIV pre-exposure prophylaxis. We evaluated safety, pharmacokinetics and pharmacodynamics of PC-6500 (0.1% GRFT in a carrageenan (CG) gel) in healthy, HIV-negative, non-pregnant women following once daily vaginal gel administration for 14 days. No significant adverse events, histopathological changes in cervico-vaginal mucosa, or anti-drug (GRFT) antibodies were detected. No cervicovaginal proinflammatory responses and no changes in the ectocervical transcriptome were evident. Vaginal microbiome remained largely unchanged. Reduced abundance of vaginosis-associated bacteria and decreased levels of proinflammatory chemokines (CXCL8 and CCL20) were observed. GRFT was not detected in plasma. GRFT and GRFT/CG in CVLs dose-dependently inhibited HIV and HPV, respectively, in vitro. The data suggest GRFT/CG is a promising on-demand multipurpose prevention product that warrants further investigation.
2021-10-04 | GSE141478 | GEO
Project description:Cervico-Vaginal Microbiome Dynamics Across HPV-Driven Lesion Stages in Moroccan Women
| PRJNA1262983 | ENA
Project description:Human associated vaginal and penile microbiome Metagenome
Project description:Clinical treatment protocols for infertility with in vitro fertilization-embryo transfer (IVF-ET) provide a unique opportunity to assess the human vaginal microbiome in defined hormonal milieu. Herein, we have investigated the association of circulating ovarian-derived estradiol (E2) and progesterone (P4) concentrations to the vaginal microbiome. Thirty IVF-ET patients were enrolled in this study, after informed consent. Blood was drawn at four time points during the IVF-ET procedure. In addition, if a pregnancy resulted, blood was drawn at 4-to-6 weeks of gestation. The serum concentrations of E2 and P4 were measured. Vaginal swabs were obtained in different hormonal milieu. Two independent genome-based technologies (and the second assayed in two different ways) were employed to identify the vaginal microbes. The vaginal microbiome underwent a transition with a decrease in E2 (and/or a decrease in P4). Novel bacteria were found in the vagina of 33% of the women undergoing IVF-ET. Our approach has enabled the discovery of novel, previously unidentified bacterial species in the human vagina in different hormonal milieu. While the relationship of hormone concentration and vaginal microbes was found to be complex, the data support a shift in the microbiome of the human vagina during IVF-ET therapy using standard protocols. The data also set the foundation for further studies examining correlations between IVF-ET outcome and the vaginal microbiome within a larger study population.
Project description:<p>Urethral microbiome of adolescent males is designed to characterize the microbial communities resident in the urethra of young men, to identify differences in these communities as a function of race/ethnicity, circumcision status, sexual exposures, and uro-genital symptoms. We collect detailed sexual behavior and symptoms data using cellular telephones with Internet access. Specimens are routinely collected at monthly intervals, and intermittently following reported symptoms, specific sexual exposures, or identification of a sexually transmitted infection. We also collect periodic samples from the penile coronal sulcus to better characterize its relationship to the urethral micriobial communities.</p> <p>Participants are ages 14 - 17 at enrollment, and prior history of sexual exposure is not required for participation. Parental permission is obtained for each participant. The planned duration of followup is up to 4 years allowing for prospective observation of both physical and behavioral maturation from middle adolescence into young adulthood.</p> <p>The overall objectives of the project are to better characterize the healthy male urethral microbiome, and to use this information to better understand acquisition of urethritis and sexually transmitted infections, as well as chronic genital pain and prostatitis syndromes that become common among young adults.</p>
Project description:Purpose: To compare single cell transcriptional profiling (scRNAseq) of different murine genital herpes infection models with HSV1-McKrae and HSV2-186. Method: DMPA-treated WT C57BL/6 mice were infected with HSV1-McKrae, HSV2-186 or PBS intravaginally. Vaginal tissues were harvested at 5 days post infection, live cells were sorted, a minimum of 16,000 cells were used for scRNAseq. Results: By tSNE visualization of 21,633 cells across all samples, 17 distinct clusters were resolved. We found significantly increased levels of Interferons-Stimulated-Genes (ISGs) in the neutrophils potentially contributing to disease onset and progression in HSV2 genital infections. Conclusion: Our study is the first comparison between the transcriptional signature of two genital herpes model- namely HSV1 and HSV2. Generated by scRNAseq, this study would provide researchers with gene candidates associated with the disease progression and inflammation induced by genital infections with HSV1 and HSV2.
Project description:Equine Papillomavirus Type 2 (EcPV2) appears to be a causal factor for the development of genital especially penile squamous cell carcinomas (SCC) and as such have an important clinical impact on horses. However, the pathomechanisms associated with this cancer transformation are not known, yet. To analyze the host’s and viral transcriptome in EcPV2 affected horses, tissue samples were collected from horses with EcPV2-positive genital lesions as well as from healthy EcPV2-negative horses. Expression levels of host and viral genes were evaluated by RNA-Seq.