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High grade serous ovarian carcinoma (HGSOC) is the most common and aggressive ovarian malignancy. Accumulating evidence indicates that HGSOC may originate from human fallopian tube epithelial cells (FTECs), although the exact pathogen(s) and/or molecular mechanism underlying the malignant transformation of FTECs is unclear. Here we show that human papillomavirus (HPV), which could reach FTECs via retrograde menstruation or sperm-carrying, interacts with the yes-associated protein 1 (YAP1) to drive the malignant transformation of FTECs. HPV prevents FTECs from natural replicative and YAP1-induced senescence, thereby promoting YAP1-induced malignant transformation of FTECs. HPV also stimulates proliferation and drives metastasis of YAP1-transformed FTECs. YAP1, in turn, stimulates the expression of the putative HPV receptors and suppresses the innate immune system to facilitate HPV acquisition. These findings provide critical clues for developing new strategies to prevent and treat HGSOC. Synopsis: Human papillomavirus (HPV) and hyperactivated YAP1 form a YAP1-HPV oncogenic alliance to drive the malignant transformation of fallopian tube epithelial cells and the initiation of high grade serous ovarian carcinoma (HGSOC). High-risk HPV and hyperactivated YAP1 drive the malignant transformation of fallopian tube epithelial cells. High-risk HPV aids YAP1 oncogenic activities by overriding oncogene-induced senescence. Hyperactivated YAP1 facilitates HPV infection by increasing HPV receptors and suppressing innate immunity. HPV is a neglected preventable ovarian cancer risk factor. Human papillomavirus (HPV) and hyperactivated YAP1 form a YAP1-HPV oncogenic alliance to drive the malignant transformation of fallopian tube epithelial cells and the initiation of high grade serous ovarian carcinoma (HGSOC). [ABSTRACT FROM AUTHOR]

BACKGROUND: Prebiotics, such as algal polysaccharides, can be used to manage metabolic diseases by modulating gut microbiota. However, the effect of Pyropia yezoensis porphyran (PYP), a red algal polysaccharide, on gut microbiota has not been reported. Thus, the objective of this study was to determine effects of PYP on metabolic disorders caused by high sucrose (HS) and underlying mechanisms involved in such effects. RESULTS: Biochemical analysis demonstrated that an HS diet increased triglyceride and circulating sugar contents (metabolic abnormalities) in Drosophila larvae. It also increased the relative abundance of harmful microbiota within the larvae as identified by 16S ribosomal DNA analysis. PYP supplementation at 25 and 50 g kg−1 equivalently reduced metabolic abnormalities in the HS group. Therefore, 25 g kg−1 PYP was selected to investigate its effects on the metabolic pathway and gut microbiota of larvae in the HS group. The activity of PYP in ameliorating metabolic abnormalities by reverse transcription quantitative real‐time polymerase chain reaction analysis was consistent with the expression trend of key factors involved in metabolism regulation. PYP reduced the relative abundance of bacteria causing metabolic abnormalities, such as Escherichia–Shigella and Fusobacterium, but increased the relative abundance of beneficial bacteria such as Bacillus and Akkermansia. However, PYP had no effect on triglyceride and circulating sugar contents in HS‐fed larvae treated with a mixture of antibiotics designed to remove gut microbiota. CONCLUSION: PYP exhibits anti‐metabolic disorder activity by modulating gut microbiota, thereby supporting the development of PYP as a functional prebiotic derived from red algae food. Copyright © 2022 John Wiley & Sons, Ltd. © 2022 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Lipid accumulation is a major factor in the development of non‐alcoholic fatty liver disease (NAFLD). Currently, there is a lack of intervention or therapeutic drugs against NAFLD. In this study, we investigated the ability of Sargassum fusiforme polysaccharide (SFPS) to reduce lipid accumulation induced by high sugar in HepG2 cells and Drosophila melanogaster larvae. The results indicated that SFPS significantly (p <.01) decreased the accumulation of lipid droplets in high sugar–induced HepG2 cells. Furthermore, SFPS also suppressed the expression of Srebp and Fas (genes involved in lipogenesis) and increased the expression of PPARɑ and Cpt1 (genes that participated in fatty acid β‐oxidation) in these cells. SFPS markedly reduced the content of triglyceride of the third instar larvae developed from D. melanogaster eggs reared on the high‐sucrose diet. The expression of the Srebp and Fas genes in the larvae was also inhibited whereas the expression of two genes involved in the β‐oxidation of fatty acids, Acox57D‐d and Fabp, was increased in the larval fat body (a functional homolog of the human liver). We also found that SFPS ameliorated developmental abnormalities induced by the high‐sucrose diet. These results of this study suggest that SFPS could potentially be used as a therapeutic agent for the prevention and treatment of NAFLD. [ABSTRACT FROM AUTHOR]