Chrysophanol inhibits the progression of gastric cancer by activating nod-like receptor protein-3

Aim:Gastric cancer(GC)is one of the most common malignant tumors.Chrysophanol has been reported to possess antitumor effects on a variety of cancers;however,its role in GC remains unclear.This study aimed to investigate the effects of chrysophanol on the proliferation,pyroptosis,migration,and invasion of GC cells.Methods:Human GC cell lines MKN 28 and AGS cells were treated with different concentrations of chrysophanol,then cell proliferation,migration,invasion and pyroptosis were determined by CCK-8,colony-forming assay,wound healing assay,Transwell assay,and flow cytometry.Cell migration and invasion were reassessed in these transfected cells following the transfection of nod-like receptor protein-3(NLRP3)siRNA in MKN 28 and AGS cells.To examine the downstream signaling pathway of the NLRP3 signaling pathway,NLRP3,caspase-1,gasdermin-D,interleukin(IL)-1β,and IL-18 were detected by quantitative real-time-polymerase chain reaction or western blotting.Results:Chrysophanol inhibited the proliferation of GC cells,caused pyroptosis,inhibited cell migration and invasion,and increased the expression of NLRP3 inflammasomes in GC cells.Knockdown of NLRP3 inhibited the effects of chrysophanol on proliferation,pyroptosis,migration,and invasion of GC cells.Chrysophanol plays an anticancer role by enhancing NLRP3.Conclusions:Chrysophanol exerts anti-neoplastic effects in vitro in GC cells by modulating NLRP3,thus highlighting its therapeutic potential in GC.

Generation of Tripotent Neural Progenitor Cells from Rat Embryonic Stem Cells

Rat is a valuable model for pharmacological and physiological studies. Germline-competent rat embryonic stem （rES） cell lines have been successfully established and the molecular networks maintaining the self-renewing, undifferentiated state of rES cells have also been well uncovered. However, little is known about the differentiation strategies and the underlying mechanisms of how these authentic rat pluripotent stem ceils give rise to specific cell types. The aim of this study is to investigate the neural differentiation capacity of rES cells. By means of a modified procedure based on previous publications - combination of mitogen-activated protein kinase （MAPK） and glycogen synthase kinase 3 （GSK3） inhibitors （two inhibitors, ＂2i＂） with feeder-conditioned medium, we successfully obtained high- quality rat embryoid bodies （rEBs） from rES cells and then differentiated them to tripotent neural progenitors. These rES cell-derived neural progenitor cells （rNPCs） were capable of self-renewing and giving rise to all three neural lineages, including astrocytes, oligo- dendrocytes, and neurons. Besides, these rES cell-derived neurons stained positive for y-aminobutyric acid （GABA） and tyrosine hydroxylase （TH）. In summary, we develop an experimental system for differentiating rES cells to tripotent neural progenitors, which may provide a powerful tool for pharmacological test and a valuable platform for studying the pathogenesis of many neurodegenerative disorders such as Parkinson＇s disease and the development of rat nervous system.

Derivation of Non-Integration Induced Pluripotent Stem Cells from Fibroblast of Severe Deafness Patients with GJB2 Mutation

In all the connexin-associated human diseases, deafness is one of the most important diseases with high frequency. The mu- tations of GJB2 （gap junction protein β2, also called connexin 26, Cx26） gene link with nonsyndromic or syndromic senso- rineural hearing loss and were shown to account for a large proportion of congenital deaf cases in many studied populations （del Castillo and del Castillo, 2011）. For example, the 235de1C mutation in GJB2 shows the frequency of approximately 1% and is the most frequent mutation in East Asian population （Yan et al., 2003）. Many efforts have been put to study the function of Gjb2 gene in both mouse model and human. In mouse, extensive deletion of Gjb2 causes embryo lethal due to the decreased transplacental glucose uptake, which was not found in human （Takata and Hirano, 1997; Gabriel et al., 1998）. In human, GJB2 deficiency is not able to cause embryo lethal （D＇Andrea et al., 2002）. However, the study of GJB2-associated hearing loss is hampered by many difficulties, such as unobtainable human cochlea and acoustic nerve tissues, and therefore the GJB2-associated hearing loss are underlying mechanisms of still remaining unclear.

Regulatory network and genetic interactions established by OsMADS34 in rice inflorescence and spikelet morphogenesis

Grasses display highly diversified inflorescence architectures that differ in the arrangement of spikelets and flowers and determine cereal yields. However, the molecular basis underlying grass inflorescence morphogenesis remains largely unknown. Here we investigate the role of a functionally diversified SEPALLATA MADS-box transcription factor, OsMADS34, in regulating rice （Oryza sativa L.） inflorescence and spikelet development. Microarray analysis showed that, at the very early stages of inflorescence formation, dysfunction of OsMADS34 caused altered expression of 379 genes that are associated with protein modification and degradation, transcriptional regulation, signaling and metabolism activity. Genetic analysis revealed that OsMADS34 controls different aspects of inflorescence structure, branching and meristem activity synergistically with LAX PANICLE1 （LAX1） and FLORAL ORGAN NUMBER4 （FON4）, as evidenced by the enhanced phenotypes of osmads34 lax1 and osmads34 fon4 compared with the single mutants. Additionally, double mutant between osmads34 and the sterile lemma defective mutant elongated empty glume （ele） displayed an enhanced phenotype, that is, longer and wider sterile lemmas that were converted into lemma/palea-like organs, suggesting that ELE and OsMADS34 synergistically control the sterile lemma development. OsMADS34 may act together with OsMADS15 in controlling sterile lemma development. Collectively, these findings provide insights into the regulatory function of OsMADS34 in rice inflorescence and spikelet development.