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Background: Acute liver failure (ALF) is one of the most common life-threatening diseases in adults without previous liver disease. Glycogen synthase kinase 3β (GSK3β) is a serine/threonine protein kinase that is widely distributed in the cells. Inhibition of its activity can inhibit cell death and promote autophagy through various pathways, thus providing a protective effect. In this study, we aimed to investigate the effect on ALF after inhibition of GSK3β and its potential mechanisms. Methods: D- galactosamine(D-Gal) in combination with lipopolysaccharide(LPS) was used to induce ALF in vitro and in vivo. And then GSK3β inhibitor TDZD-8 was used to explore the protective effect against ALF. After TDZD-8 treatment TUNEL staining and flow techniques were used to detect the proportion of apoptosis in liver tissues and cells respectively, while western blotting and immunofluorescence assays were performed to detect the expression levels of apoptosis, pyroptosis and necroptosis-related proteins in tissues and cells. In addition, western blotting was performed to explore the specific mechanism of hepatoprotective effect after GSK3β inhibition to detect the expression levels of TAK1, TRAF6 and HDAC3 after TRAF6 and HDAC3 inhibition alone. The co-localization of TRAF6 and HDAC3 in vitro was detected by immunofluorescence, while the interaction between TRAF6 and HDAC3 was detected by immunoprecipitation assay. Results: Both in vivo and in vitro experiments, GSK3β inhibitor TDZD-8 can significantly alleviate the progression of ALF. Inhibition of GSK3β activity could significantly reduce the level of hepatocyte apoptosis, pyroptosis, necroptosis and improve liver dysfunction and tissue damage. Furthermore, we found that hepatocyte TAK1 and TRAF6 levels decreased and HDAC3 levels increased in ALF, whereas inhibition of GSK3β upregulated TAK1 and TRAF6 levels and decreased HDAC3 expression. Conclusion: GSK3β inhibitor TDZD-8 can prevent the progression of ALF, and its action may involve the TRAF6/HDAC3/TAK1 pathway. [ABSTRACT FROM AUTHOR]

Developmentally programmed cell death (dPCD) is a tightly controlled biological process. In recent years, vital roles of dPCD on regulating floral organ growth and development have been reported. It is well known that flower is an essential organ for reproduction and a turning point of plants' life cycle. Hence, uncovering the complex molecular networks which regulates dPCD processes in floral organs is utmost important. So far, our understanding of dPCD on floral organ growth and development is just starting. Herein, we summarize the important factors that involved in the tapetal degeneration, pollen tube rupture, receptive synergid cell death, nucellar degradation, and antipodal cell degradation. Meanwhile, the known factors that involved in transmitting tract formation and self-incompatibility-induced PCD were also introduced. Furthermore, the genes that associated with anther dehiscence and petal senescence and abscission were reviewed as well. The functions of various types of factors involved in floral dPCD processes are highlighted principally. The regulatory panorama described here can provide us some insights about flower-specific dPCD process. • Developmentally programmed cell death (dPCD) plays essential roles in floral organ growth, development, and senescence. • dPCD process was observed in nine types of floral organs. • Regulatory networks of dPCD in floral organs were delineated in this review. [ABSTRACT FROM AUTHOR]

Monocarpic plants have a single reproductive phase, in which their longevity is developmentally programmed by molecular networks. In the reproductive phase of Arabidopsis thaliana , the inflorescence meristem (IM) maintains a central pool of stem cells and produces a limited number of flower primordia, which result in seed formation and the death of the whole plant. In this study, we observed morphological changes in the IM at cellular and intracellular resolutions until the end of the plant life cycle. We observed four biological events during the periods from 1 week after bolting (WAB) till the death of stem cells: (1) the gradual reduction in the size of the IM, (2) the dynamic vacuolation of IM cells, (3) the loss of the expression of the stem cell determinant WUSCHEL (WUS), and (4) the upregulation of the programmed cell death marker BIFUNCTIONAL NUCLEASE1 (BFN1) in association with the death of stem cells. These results indicate that the stem cell population gradually decreases in IM during plant aging and eventually is fully terminated. We further show that the expression of WUS became undetectable in IM at 3 WAB prior to the loss of CLAVATA3 (CLV3) expression at 5 WAB; CLV3 is a negative regulator of WUS. Moreover, clv3 plants showed delayed loss of WUS and lived 6 weeks longer compared with wild-type plants. These results indicated that the prolonged expression of CLV3 at 4–5 WAB may be a safeguard that inhibits the reactivation of WUS and promotes plant death. Finally, through transcriptome analysis, we determined that reactive oxygen species (ROS) are involved in the control of plant longevity. Our work presents a morphological and physiological framework for the regulation of plant longevity in Arabidopsis. [ABSTRACT FROM AUTHOR]

Programmed cell death (PCD) play essential roles in plant growth and development. Stigmatic papilla cells form an indispensable organ for plant reproduction. The lifetime of papilla cells is tightly controlled, and the developmental PCD (dPCD) process is involved in papilla cell death. Hence, papilla cell death is a good model for studying on PCD process. In this study, the dPCD signal was visualized in dying papilla cells by detecting the GUS signal of the PCD-related reporter gene BIFUNCTIONAL NUCLEASE 1 (BFN1). We found that the GUS was not expressed at young stage, but strongly expressed in papilla cells at the ageing stage, indicating the PCD process was triggered to terminate the papilla cell fate. Given this, the RNA-Seq data set, which covered the information of the whole lifespan of papilla cells, was analyzed aiming to understand which genes and pathways were involved in papilla cell death. 37 differential expressed genes (DEGs) were isolated. Moreover, the pathways related to energy production and transportation, autophagy, and plant hormone signal transduction were considered as the key pathways involved in the papilla cell death. 9 types, total of 104 transcriptional factors (TFs) were identified as well. Finally, a putative working model of papilla cell death was integrated. The findings herein will enrich the knowledge of the dPCD-mediated pathway in regulating plant organ/tissue growth, development, senescence, and death. Our study will provide some referential gene resources for studying on the dPCD in other plant organs or tissues. • Papilla cell is a good model for study on programmed cell death (PCD). • Total of 37 DEGs involved in regulating papilla cell PCD were screened out. • Nine types, total of 104 TFs involved in regulating papilla cell PCD were isolated. • A feasible networking model of papilla cell PCD was generated. [ABSTRACT FROM AUTHOR]