CRK41 Modulates Microtubule Depolymerization in Response to Salt Stress in Arabidopsis.

The pivotal role of cysteine-rich receptor-like kinases (CRKs) in modulating growth, development, and responses to stress has been widely acknowledged in Arabidopsis. However, the function and regulation of CRK41 has remained unclear. In this study, we demonstrate that CRK41 is critical for modulating microtubule depolymerization in response to salt stress. The crk41 mutant exhibited increased tolerance, while overexpression of CRK41 led to hypersensitivity to salt. Further analysis revealed that CRK41 interacts directly with the MAP kinase3 (MPK3), but not with MPK6. Inactivation of either MPK3 or MPK6 could abrogate the salt tolerance of the crk41 mutant. Upon NaCl treatment, microtubule depolymerization was heightened in the crk41 mutant, yet alleviated in the crk41mpk3 and crk41mpk6 double mutants, indicating that CRK41 suppresses MAPK-mediated microtubule depolymerizations. Collectively, these results reveal that CRK41 plays a crucial role in regulating microtubule depolymerization triggered by salt stress through coordination with MPK3/MPK6 signalling pathways, which are key factors in maintaining microtubule stability and conferring salt stress resistance in plants.

Gut-Flora-Dependent Metabolite Trimethylamine-N-Oxide Promotes Atherosclerosis-Associated Inflammation Responses by Indirect ROS Stimulation and Signaling Involving AMPK and SIRT1.

Trimethylamine-N-oxide (TMAO), a gut-microbiota-dependent metabolite after ingesting dietary choline, has been identified as a novel risk factor for atherosclerosis through inducing vascular inflammation. However, the underlying molecular mechanism is poorly understood. Using an in vitro vascular cellular model, we found that the TMAO-induced inflammation responses were correlated with an elevation of ROS levels and downregulation of SIRT1 expression in VSMCs and HUVECs. The overexpression of SIRT1 could abrogate both the stimulation of ROS and inflammation. Further studies revealed that AMPK was also suppressed by TMAO and was a mediator upstream of SIRT1. Activation of AMPK by AICAR could reduce TMAO-induced ROS and inflammation. Moreover, the GSH precursor NAC could attenuate TMAO-induced inflammation. In vivo studies with mice models also showed that choline-induced production of TMAO and the associated glycolipid metabolic changes leading to atherosclerosis could be relieved by NAC and a probiotic LP8198. Collectively, the present study revealed an unrecognized mechanistic link between TMAO and atherosclerosis risk, and probiotics ameliorated TMAO-induced atherosclerosis through affecting the gut microbiota. Consistent with previous studies, our data confirmed that TMAO could stimulate inflammation by modulating cellular ROS levels. However, this was not due to direct cytotoxicity but through complex signaling pathways involving AMPK and SIRT1.

Gut Microbiota Approach-A New Strategy to Treat Parkinson's Disease.

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by neuronal loss and dysfunction of dopaminergic neurons located in the substantia nigra, which contain a variety of misfolded α-synuclein (α-syn). Medications that increase or substitute for dopamine can be used for the treatment of PD. Recently, numerous studies have shown gut microbiota plays a crucial role in regulating and maintaining multiple aspects of host physiology including host metabolism and neurodevelopment. In this review article, the role of gut microbiota in the etiological mechanism of PD will be reviewed. Furthermore, we discussed current pharmaceutical medicine-based methods to prevent and treat PD, followed by describing specific strains that affect the host brain function through the gut-brain axis. We explained in detail how gut microbiota directly produces neurotransmitters or regulate the host biosynthesis of neurotransmitters. The neurotransmitters secreted by the intestinal lumen bacteria may induce epithelial cells to release molecules that, in turn, can regulate neural signaling in the enteric nervous system and subsequently control brain function and behavior through the brain-gut axis. Finally, we proved that the microbial regulation of the host neuronal system. Endogenous α-syn can be transmitted long distance and bidirectional between ENS and brain through the circulatory system which gives us a new option that the possibility of altering the community of gut microbiota in completely new medication option for treating PD.

Clinicopathological and prognostic implications of polo-like kinase 1 expression in colorectal cancer: A systematic review and meta-analysis.

BACKGROUND: Polo-like kinase 1 (PLK1) is a potential prognostic marker in colorectal cancer (CRC). Nevertheless, the clinicopathological and prognostic roles of PLK1 in CRC are still undefined. Therefore, we performed a meta-analysis to investigate the clinicopathological and prognostic relevance of PLK1 expression in CRC patients. METHODS: Studies published between 2003 and 2016 were selected for the meta-analysis based on an electronic literature search (PubMed, EMBASE and Chinese databases). Studies that investigated the clinicopathological and prognostic impacts of PLK1 expression in CRC patients were included for this analysis. RESULTS: Eleven studies that enrolled 1147 CRC patients were included in our meta-analysis. The effect of PLK1 level on overall survival (OS) was reported in five studies, which included 702 patients. Ten studies investigated the clinicopathological role of PLK1 expression in CRC patients. Consequently, PLK1 overexpression was associated with poorer OS in CRC patients. Furthermore, the results revealed that higher PLK1 levels were also observed in CRC tissues compared with that of normal colorectal tissues. In addition, this meta-analysis also revealed positive correlations between PLK1 upregulation and lymph node metastasis or invasion. PLK1 overexpression was significantly correlated with advanced TNM stages and higher Dukes stages. CONCLUSION: This meta-analysis strongly supports the hypothesis that PLK1 might serve as an important factor in evaluating the biological behavior and prognosis of CRC.

Long noncoding RNAs in autoimmune diseases.

With the completion of the human genome project and further development of high-throughput genomic technologies, interest in long noncoding RNAs (lncRNAs), which are defined as non-protein-coding RNAs at least 200 nucleotides in length, has strongly increased, and lncRNAs have become a major research direction. Increasing evidence demonstrates that lncRNAs are closely related to human growth and development and to disease occurrence via various mechanisms. lncRNAs also play crucial roles in the differentiation and activation of immune cells, and their relationships with human autoimmune diseases have received increasing attention. The development of biotechnology has led to the gradual discovery of many potential lncRNA functions. In this review, we discuss various lncRNAs that have been implicated in different human autoimmune diseases, focusing on their clinical applications as potential biomarkers and therapeutic targets in the pathologies of diverse human autoimmune diseases. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 468-475, 2019.