A multifaceted analysis of OTUD5 integrated MAVS in innate immunity of Primary Biliary Cholangitis

by Ran Chen, Yan Sun, Wenlin Tai

Background

Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease characterized by cholestasis caused by intrahepatic small bile duct injury. Promoting the molecular mechanism of OTU deubiquitinase 5 (OTUD5) in the treatment of PBC requires further exploration. This study unraveled the molecular underpinnings of PBC through bio-informatics analysis and experimental verification for the development of targeted therapeutic strategies.

Methods

This study screened immune-related genes and validated their expression patterns in whole blood of patients with PBC using microarray based on GEO datasets. The expression level of OTU deubiquitinase 5 (OTUD5) was validated in peripheral blood samples using RT-qPCR and immunofluorescence. Subsequently, proteomic bioinformatics analyses were conducted utilizing STRING and InBio Discover databases to predict interactions with the mitochondrial antiviral signalling protein (MAVS). Furthermore, immunochemical and immunofluorescence analyses of MAVS expression in liver tissues were conducted with a thorough analysis of immune cell infiltration specific to the disease by utilizing single-cell RNA sequencing (scRNA-seq) technology in peripheral blood mononuclear cells (PBMCs) derived from both patients with PBC and healthy controls.

Results

Compared with those of healthy controls, the liver tissues of patients with PBC presented increased NK cell activation, monocyte/mast cell numbers, and eosinophil numbers. Compared with those in 10 healthy controls, the expression of OTUD5 and MAVS was increased in 16 tissues of patients with PBC. High expression of OTUD5-MAVS in subpopulation 11 mononuclear macrophages was screened by PBMC scRNA-seq, and mononuclear cells with the subgroup 11 phenotype presented highly differentiated characteristics. The expression of OTUD5 and MAVS was inhibited in RAW264.7 cells when OTUD5 was knocked down (P  Conclusion

This study focused on the overexpression of OTUD5 and its interaction with MAVS within macrophage subset 11 in patients with primary biliary cholangitis (PBC). The expression of OTUD5 and MAVS is increased in patients with PBC and is a potential target for the diagnosis and treatment of PBC.

Concentration-dependent effects of fermented spent coffee grounds and contrasting effects of earthworms on growth and phytochemicals in medicinal plant <i>Glechoma longituba</i>

by Bing-Nan Zhao, Zi-Yang Xie, Jia-Ning Liu, Xiao-Ran Chen, Xin-Xin Wang, Jia-Yi Li, Rui Zhang, Chao Si

Fermented spent coffee grounds (FSCG) serve as a valuable soil amendment to improve soil structure and fertility, while earthworms play a well-established role in enhancing soil processes and plant growth. However, their combined effects on bioactive compound accumulation in medicinal plants remain unclear. This study investigated the individual and interactive effects of FSCG (0%, 10%, and 20%, v/v) and earthworms (with and without Pheretima guillelmi) on the growth and phytochemical content of Glechoma longituba, a common medicinal herb, under greenhouse conditions. Results showed that 10% FSCG generally promoted plant growth, whereas 20% FSCG generally enhanced the accumulation of total flavonoids, chlorogenic acid, and soluble protein. Earthworms enhanced aboveground biomass and node number but significantly reduced chlorogenic acid content. These findings highlight the potential of FSCG as a sustainable soil amendment in medicinal plant cultivation and underscore the need to consider earthworm activity when optimizing both plant biomass and phytochemical quality.