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Introduction: Yes-associated protein 1 (YAP1) is a crucial molecule in the Hippo pathway. The impact of hepatocyte-specific Yap1 knockout (Yap1LKO) on hepatic lipid droplets (LD) and pePLIN2 in metabolic fatty liver has not been reported. This study aims to explore whether Yap1LKO could offer a protective effect in a liver injury model. Methods: Three-week-old Yap1LKO and Yap1Flox mice were given aristolochic acid I (AAI) combined carbon tetrachloride (CCL4) establish liver injury model. Eight-week-old Yap1LKO and Yap1Flox mice were fed with a high-fat diet for 18 weeks to establish obesity-related liver injury model. Further biochemical, histomorphological, immunohistochemical, and lipidomic analyses were performed on serum and liver tissues of these mice to elucidate the effects of hepatocyte-specific Yap1 knockout on hepatic lipid metabolism. Results: Yap1LKO reduced triglyceride (TG) content and PLIN2 expression level in the liver during the intervention of AAI combined CCl4. Moreover, Yap1LKO improved lipid metabolism homeostasis in the liver by increasing the beneficial lipid molecules and reducing the harmful lipid molecules through lipidomics. Finally, Yap1LKO reduced TG content in the serum and liver, hepatic vacuolar degeneration, and hepatic PLIN2 expression level in mice fed with a high-fat diet (HFD). Conclusion: Yap1LKO is protective in regulating liver and blood TG when induced with toxic substances AAI combined CCl4 and a high-fat diet. [ABSTRACT FROM AUTHOR]

The efficacy of anti‐PD‐1 therapy is not as expected in hepatocellular carcinoma (HCC). YAP1 was overexpressed and activated in HCC. The mechanism of YAP1 in HCC immune escape is unclear. Anti‐PD‐1 treatment increased YAP1 expression in liver tumor cells, and exhausted CD4+ and CD8+ T cells in the blood and spleen of liver tumor mice. YAP1 knockdown suppressed PD‐L1 expression, which was involved in JAK1/STAT1, 3 pathways. Moreover, Yap1 knockout elevated CD4+ and CD8+ T cells in liver tumor niche. Consistently, verteporfin, YAP1 inhibitor, decreased TGF‐β and IFN‐γ in liver tumor niche and exhausted CD8+ T cell in the spleen. DHA suppressed YAP1 expression and break immune evasion in liver tumor niche, characterized by decreased PD‐L1 in liver tumor cells and increased CD8+ T cell infiltration. Furthermore, DHA combined with anti‐PD‐1 treatment promoted CD4+ T cell infiltration in the spleen and CD8+ T cell in tumor tissues of mice. In summary, YAP1 knockdown in liver tumor cells suppressed PD‐L1 expression and recruited cytotoxic T lymphocytes (CTLs), leading to break immune evasion in tumor niche. Mechanistically, YAP1 knockdown suppressed PD‐L1 expression, which was involved in JAK1/STAT1, 3 pathways. Finally, DHA inhibited YAP1 expression, which not only inhibited liver tumor proliferation but also break the immunosuppressive niche in liver tumor tissues and improve the effect of anti‐PD‐1 therapy. [ABSTRACT FROM AUTHOR]

Drug-induced liver injury (DILI) by acetaminophen (APAP) was one of the most challenging liver diseases. Wolfberry (Lycium barbarum L.), a traditional Chinese medicinal material and food supplement, has a potential effect on increasing the abundance of Akkermansia muciniphila (A. muciniphila) in mice colons. However, the effect and mechanism of wolfberry remain unclear in APAP-induced DILI. In this study, wolfberry promoted the proliferation of activated-A. muciniphila in vitro and in vivo. For the first time, we detected that the activated-A. muciniphila but not the killed-A. muciniphila increased the expression level of Yes-associated protein 1 (YAP1) in the liver and alleviated liver injury in APAP-induced DILI mice. Mechanically, A. muciniphila improved the intestinal mucosal barrier and reduced lipopolysaccharide (LPS) content in the liver, leading to the increased expression level of YAP1. Furthermore, wolfberry increased the A. muciniphila abundance in the colon and YAP1 expression in the liver from APAP-induced DILI mice, which promoted the recovery of APAP-induced liver injury. Meanwhile, wolfberry combination with A. muciniphila synergistically increased AKK abundance and YAP1 expression in the liver. Our research provides an innovative strategy to improve DILI., (© 2022 Federation of American Societies for Experimental Biology.)

Objective: To analyse the saliva microbial abundance and composition by 16s rRNA sequence during Helicobacter pylori (H.pylori) eradication., Study Design: Descriptive study., Place and Duration of Study: Hebei University of Chinese Medicine, Hebei Provincial Hospital of Traditional Chinese Medicine, from March 2019 to January 2020., Methodology: The saliva microbial were analysed before and after the bismuth-containing quadruple therapy. A total of ten saliva samples (three groups) were enrolled in the study. The authors used the linear discriminant analysis effect size (LEfSe) method and Welch's t-test for comparative analysis to identify which taxa could be significantly affected in three groups., Results: H.pylori 16S rRNA gene sequence was not detected in the ten saliva samples. The abundance of Prevotella_sp._oral_clone_P4PB_83_P2 from healthy adults was higher than H.pylori-positive patients. Moreover, after the bismuth-containing quadruple therapy, the diversity and richness of saliva bacteria reduced. Lautropia, Burkholderiales, uncultured bacterium, Burkholderiaceae, and Actinomyces were enriched in H.pylori-positive patient samples after the bismuth-containing quadruple therapy., Conclusion: The diversity and richness of salivary microbiome were reduced in H.pylori-positive patient, and bismuth-containing quadruple therapy affected oral microbiota. Key Words: Helicobacter pylori, Saliva, Microbiota, RNA, Bismuth.