Vaginal microbiota diversity and paucity of Lactobacillus species are associated with persistent hrHPV infection in HIV negative but not in HIV positive women
SCIENTIFIC REPORTS
Authors: Dareng, Eileen O.; Ma, Bing; Adebamowo, Sally N.; Famooto, Ayotunde; Ravel, Jacques; Pharoah, Paul P.; Adebamowo, Clement A.
Abstract
The vaginal microbiota is thought to play a role in modulating risk of high-risk human papillomavirus (hrHPV) infection. We examined the relationship between the vaginal microbiota and persistent hrHPV infection in HIV-negative and HIV-positive women. We used 16S-rRNA sequencing to characterize the vaginal microbiota of two serial samples taken six months apart from 211 Nigerian women (67%, 142/211 HIV-positive and 33%, 69/211 HIV-negative) and evaluated the association between the vaginal microbiota and persistent hrHPV infection using generalized estimating equation logistic regression models and linear discriminant analysis effect size (LEfSe) algorithm to identify phylotypic biomarkers of persistent hrHPV infection. The high diversity microbiota, Community State Type IV-B, was the most prevalent in both HIV-negative (38% at baseline, 30% at the follow-up visit) and HIV-positive (27% at baseline, 35% at the follow-up visit) women. The relationship between the vaginal microbiota and persistent hrHPV was modified by HIV status. In HIV-negative women, women with Lactobacillus dominant microbiota had lower odds (OR: 0.35, 95% CI 0.14-0.89, p = 0.03) of persistent hrHPV compared to women with Lactobacillus deficient microbiota. While among HIV-positive women, the odds of being persistently infected with hrHPV was higher in women with Lactobacillus dominant microbiota (OR: 1.25, 95% CI 0.73-2.14 p = 0.41). This difference in effect estimates by HIV was statistically significant (p = 0.02). A high diversity vaginal microbial community with paucity of Lactobacillus species was associated with persistent hrHPV infection in HIV-negative women but not in HIV-positive women.
Fucoxanthin may inhibit cervical cancer cell proliferation via downregulation of HIST1H3D
JOURNAL OF INTERNATIONAL MEDICAL RESEARCH
Authors: Ye, Guoliu; Wang, Lingling; Yang, Kang; Wang, Caizhi
Abstract
Objective To investigate the role of fucoxanthin, reported to have significant anticancer effects, and histone Cluster 1 H3 Family Member D (HIST1H3D; implicated in tumorigenesis) in cervical cancer. Methods The half maximal inhibitory concentration (IC50) of fucoxanthin against HeLa and SiHa cervical cancer cells was determined. Differentially expressed genes (DEGs) in SiHa cells treated with IC50 fucoxanthin were screened by high-throughput techniques and subjected to signal enrichment. Following identification ofHIST1H3Das a candidate gene, HIST1H3D-knockdown models were created via transfection with a short hairpin HIST1H3D payload. Impacts on cell proliferation, cell-cycle distribution, colony formation, and apoptosis were studied. Results The fucoxanthin IC50 was 1 445 and 1 641 mu M (Hela and SiHa cells, respectively). Chip results revealed 2 255 DEGs, including 943 upregulated and 1 312 downregulated genes, in fucoxanthin-treated versus untreated SiHa cells. Disease and function analysis indicated that these DEGs are primarily associated with cancer and organismal injuries and abnormalities, and online integrated pathway analysis showed that the DEGs were mainly enriched in p53 signalling. HIST1H3D was significantly downregulated in response to fucoxanthin. Inhibition of HIST1H3D mRNA significantly reduced cell proliferation and colony formation, significantly augmented the percentage of apoptotic HeLa and SiHa cells, and cells were arrested in G(0)/G(1)cell cycle phase. Conclusion The results suggest thatHIST1H3Dmay be an oncogene in cervical carcinogenesis and a potential fucoxanthin target in treating cervical cancer.