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Zuo, L.

Publications and source records attributed to Zuo, L..

3 recordsLinked to original sources
bioRxiv2020

Rottlerin ameliorates DSS-induced colitis by improving intestinal barrier function via activation of the Epac-2/Rap-1 signaling pathway.

OBJECTIVESRottlerin, a pan PDE inhibitor, has a variety of pharmacological activities, including enhancing barrier function and mediating anti-inflammatory activity by changing the distribution of occludin and ZO-1. Nevertheless, the function of rottlerin on Crohn disease (CD) keep unknown. Our aim of the study is to investigate the role of rottlerin on CD-like colitis and its mechanism. METHODSWild-type mice which were 8-10 weeks old were randomly divided into three treatment groups: (i) the normal feeding, no administration (control) group, (ii) the group administered 3% dextran sodium sulfate (DSS) alone, and (iii) the group administered rottlerin (100 mg/kg) and 3% DSS. In this study, the effect of rottlerin on the function and structure of the intestinal barrier was investigated, and the possible mechanism was discussed. We performed signaling pathway analysis and flow cytometry to identify the detailed mechanisms by which rottlerin (10 g/mL) treatment inhibits cell growth arrest and the attenuation of TJ proteins in LPS-treated FHs 74 int cells. RESULTSRottlerin treatment significantly ameliorated colitis induced by DSS in WT mice, which was manifested by a decrease in inflammation score, the attenuation of inflammatory factors and the inhibition of destruction on intestinal barrier structure. Rottlerin enhanced the levels of occludin and ZO-1, and improved the function of intestinal barrier, which may have been why rottlerin ameliorated colitis in WT mice. The anti-inflammatory effect of rottlerin may be partly due to the activation of Epac-2/Rap-1 signaling. CONCLUSIONSRottlerin may treat CD in humans via enhancing TJ proteins expression and improving the function of intestinal barrier.

cell biology↗
bioRxiv2020

Genetic structure, function and evolution of capsule biosynthesis loci in Vibrio parahaemolyticus

Capsule-forming extracellular polysaccharides are crucial to bacterial host colonization, invasion, immune evasion and ultimately pathogenicity. Due to warming ocean waters and human encroachment of coastal ecosystems, Vibrio parahaemolyticus has emerged as a globally important food-borne enteropathogen implicated in acute gastroenteritis, wound infections, and septic shock. Conventionally, the antigenic properties of lipopolysaccharide (LPS, O antigen) and capsular polysaccharide (CPS, K antigen) have provided a basis for serotyping V. parahaemolyticus, while disclosure of genetic elements encoding 13 O-serogroups have allowed molecular serotyping methods to be developed. However, the genetic structure of CPS loci for 71 K-serogroups has remained unidentified, limiting progress in understanding its roles in V. parahaemolyticus pathophysiology. In this study, we identified and characterized the genetic structure and their evolutionary relationship of CPS loci of 40 K-serogroups through whole genome sequencing of 443 V. parahaemolyticus strains. We found a distinct pattern of CPS gene cluster across different K-serogroups, and expanded its new right-border by identifying glpX as a key gene conserved across all serotypes. A total of 217 genes involved in CPS biosynthesis were annotated. Functional contents and genetic structure of the 40 K-serogroups were analyzed. Based on inferences from species trees and gene trees, we proposed an evolution model of the CPS gene clusters of 40 K-serogroups. Horizontal gene transfer by recombination from other Vibrio species, gene duplication and nonsense mutations are likely to play instrumental roles in the evolution of CPS in V. parahaemolyticus. It is the first time, to the best of our knowledge, that a large-scale of CPS gene clusters of different K-serogroups in V. parahaemolyticus have been identified and characterized in evolutionary contexts. This work should help advance understanding on the variation of CPS in V. parahaemolyticus, and provide a framework for developing diagnostically relevant serotyping methods. Author summaryDue to warming ocean waters and human encroachment of coastal ecosystems, Vibrio parahaemolyticus has emerged as a globally important food-borne enteropathogen. However, the genetic structure of CPS loci for 71 K-serogroups V. parahaemolyticus have remained unidentified, limiting progress in understanding its roles in V. parahaemolyticus pathophysiology. In this study, we identified and characterized the genetic structure of CPS loci of 40 K-serogroups through whole genome sequencing of 443 V. parahaemolyticus strains. We expanded and identified its new right-border by identifying glpX as a key gene conserved across all serotypes. We proposed an evolution model of the CPS gene clusters of 40 K-serogroups. We also found horizontal gene transfer by recombination from other Vibrio species, gene duplication and nonsense mutations are likely to play instrumental roles in the evolution of CPS in V. parahaemolyticus. It is the first time, to the best of our knowledge, that a large-scale of CPS loci of different K-serogroups in V. parahaemolyticus have been identified and characterized in evolutionary contexts. This work should help advance understanding on the variation of CPS in V. parahaemolyticus, and provide a framework for developing diagnostically relevant serotyping methods.

microbiology↗
bioRxiv2019

Effects of substrate stiffness on the biological behavior of human umbilical vein endothelial cells

BackgroundThe biophysical attributes of a substrate can directly influence endothelial cell behaviors. Here, we explored substrate stiffness and its biological impact on human umbilical vein endothelial cell (HUVEC) behavior, representing different anatomical sites and differentiation states in vivo.\n\nMaterial and MethodsHUVECs were cultured on both stiff substrate (25 kPa hydrogel GEL) and tissue culture plastic (TCP). Cell cytoskeleton and proliferation were detected by immunofluorescence and BrdU assays, respectively. The protein and gene expression levels of connexin 40 (CX40) were ascertained via Western blotting analysis and quantitative real-time polymerase chain reaction. Glycosaminoglycan (GAG) content was determined using a sulfated GAG detection kit.\n\nResultsResults showed that actin stress fiber density and HUVEC proliferation both decreased, whereas CX40 expression and GAG content both increased in the cells grown on the stiff substrate compared to cells grown on the TCP.\n\nConclusionsFollowing culture on the stiff substrate, the biological behavior of the HUVECs differed obviously to those cultured on the TCP. Our results suggest that the state of the cells cultured on the stiff substrate may be similar to their phenotypic state in vivo.

cell biology↗