Acute pancreatitis is characterized by zymogen preactivation. Severe inflammation caused by zymogen activation can eventually lead to multiple organ dysfunctions which contribute to the high mortality rate of severe acute pancreatitis. However, there is no specific treatment available for acute pancreatitis therapy. Here, we show that spautin-1, which effectively inhibits autophagy flux, ameliorated the pathogenesis of acute pancreatitis induced by cerulein or L-arginine. CaMKII phosphorylation due to cytosolic calcium overload was revealed in this paper. It was also demonstrated that autophagic protein aggregates degradation blockade accompanied by impaired autophagy correlated positively with intra-acinar cell digestive aymogen activation stimulated by cerulein or L-arginine. The role of spautin-1 in ameliorating acute pancreatitis was shown here to be associated with impaired autophagy inhibition and Ca 2+ overload alleviation. We provide a promising therapy for acute pancreatitis through targeting both impaired autophagy and increased cytosolic calcium.
Chinese mitten crab (Eriocheir sinensis) has the spermatozoa with typical aflagellate, decondensed chromatin, cup-shaped nuclei, and radial arms. However, the mechanism of spermatogenesis during which the specific spermatozoa are generated in this species is yet unclear. Here, the transcriptome of developing testis in E. sinensis was analyzed using the ways of RNA-seq and bioinformatics analysis to identify candidate genes potentially involved in development of testis and spermatogenesis. The Illumina HiSeq2500 sequencing of three replicons of samples produced a total of 145.19 M clean reads representing with a total of 21.34 Gb bases and 45.48% GC content. 56.30% clean reads were mapped to the draft genome of E. sinensis. The assembly of the transcriptome yielded contigs of 5691802 sequences and unigenes of 406527 sequences. Total 24246 and 40793 transcripts were annotated using Swissprot and Nr database, respectively. There were 48213 (70.31%) and 7858 (46.25%) transcripts with identity of more than 99 matching to mature testis unigenes in the databases of Nr and EST, respectively. The analytic results of KOG, GO and KEGG showed wide potential molecular functions of transcripts in the developing testes. KEGG analysis of unigenes yielded total 9422 predicted genes. Those predicted genes were involved in total 216 KEGG pathways related to the physiological activities of developing testis. 1975 predicted genes were involved in cellular and subcellular structural alteration of male germ cells. There were important roles of some pathways in the processes of morphological and structural biogenesis pertaining to testis development and spermatogenesis. Other 583 unigenes encoding the genetic and epigenetic factors also be found, which might contribute to the decondensation and stability of decondensed nuclei in the spermatozoa. These predicted events provide a view of the potential molecular mechanisms of development of testis and spermatogenesis in E. sinensis.
There is growing evidence on the clinical significance of Tumor Microenvironment (TME) cells in predicting prognosis and therapeutic effects. However, cell interactionsin tumor microenvironments have not been thoroughly studied or systematicallyanalyzed so far. In this study, 22 immune cell components in the lung adenocarcinoma(LUAD) TME were analyzed using gene expression profile from The Cancer GenomeAtlas (TCGA), Gene Expression Omnibus (GEO) . The TME based molecular subtypesof LUAD were defined to evaluate further the relationship between molecular subtypes,prognosis, and clinical characteristics. A TME risk score model was constructed byusing the differentially expressed genes (DEGs) of molecular subtypes. The relationshipbetween the TME score and clinical characteristics and genomic mutations wascompared to identify the genes that have significant associations with the TME. Thecomprehensive analysis of the TME characteristics maybe helpful in revealing theresponse of LUAD patients to immunotherapy, providing a new strategy forimmunotherapy.
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