Intravenous thrombolysis (IVT) with recombinant tissue plasminogen activator (rt-PA) within 4.5 hours is an effective and routine therapy for acute ischemic stroke (AIS). The purpose of the study was to identify predictors of functional outcome at 3 months and hemorrhagic complications after IVT. A total of 123 AIS patients treated with intravenous alteplase within 4.5 hours after stroke were enrolled. Baseline clinical characteristics, medication and disease history, radiographic and laboratory data were collected. The clinical functional outcome at 3 months was measured by the modified Rankin Scale dichotomized at 0 - 1 (favorable) vs. 2 - 6 (unfavorable). Hemorrhagic complications were measured within 36 hours after IVT. Univariate and multivariate analysis was applied in the study, and the logistic regression identified the predictors for functional outcome at 3 months and hemorrhagic complications within 36 hours. In univariate analysis, the favorable outcome was significantly associated with short hospitalization, low initial National Institute of Health Stroke Scale scores, previous smoking, previous statin use, and absence of post-stroke cerebral edema or pneumonia. Hemorrhagic complications were significantly associated with high initial NIHSS scores, low platelet count, high D-dimer level, previous atrial fibrillation, and onset seasons (except summer). Multivariate regression analyses identified that seasons (spring and summer), short hospital stays, and absence of post-stroke cerebral edema or pneumonia were the predictors of a favorable functional outcome. Meanwhile, seasons (except summer), low platelet count, and high D-dimer levels were correlation factors for prognosis of high hemorrhagic complications. .
Background: Sodium Taurocholate Co-transporting Polypeptide (NTCP) and Bile Salt Export Pump (BSEP) play significant roles as membrane transporters because of their presence in the enterohepatic circulation of bile salts. They have emerged as promising drug targets in related liver disease. Methods: We reviewed the literature published over the last 20 years with a focus on NTCP and BSEP. Results: This review summarizes the current perception about structure, function, genetic variation, and regulation of NTCP and BSEP, highlights the effects of their defects in some hepatic disorders, and discusses the application prospect of new transcriptional activators in liver diseases. Conclusion: NTCP and BSEP are important proteins for transportation and homeostasis maintenance of bile acids. Further research is needed to develop new models for determining the structure-function relationship of bile acid transporters and screening for substrates and inhibitors, as well as to gain more information about the regulatory genetic mechanisms involved in the processes of liver injury.
PurposeThe number of people with type 2 diabetes (T2D) is growing rapidly worldwide. Islet β-cell dysfunction and failure are the main causes of T2D pathological processes. The aim of this study was to elucidate the underlying pathways and coexpression networks in T2D islets.Materials and methodsWe analyzed the differentially expressed genes (DEGs) in the data set GSE41762, which contained 57 nondiabetic and 20 diabetic samples, and developed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Protein–protein interaction (PPI) network, the modules from the PPI network, and the gene annotation enrichment of modules were analyzed as well. Moreover, a weighted correlation network analysis (WGCNA) was applied to screen critical gene modules and coexpression networks and explore the biological significance.ResultsWe filtered 957 DEGs in T2D islets. Then GO and KEGG analyses identified that key pathways like inflammatory response, type B pancreatic cell differentiation, and calcium ion-dependent exocytosis were involved in human T2D. Three significant modules were filtered from the PPI network. Ribosome biogenesis, extrinsic apoptotic signaling pathway, and membrane depolarization during action potential were associated with the modules, respectively. Furthermore, coexpression network analysis by WGCNA identified 13 distinct gene modules of T2D islets and revealed four modules, which were strongly correlated with T2D and T2D biomarker hemoglobin A1c (HbA1c). Functional annotation showed that these modules mainly enriched KEGG pathways such as NF-kappa B signaling pathway, tumor necrosis factor signaling pathway, cyclic adenosine monophosphate signaling pathway, and peroxisome proliferators-activated receptor signaling pathway.ConclusionThe results provide potential gene pathways and underlying molecular mechanisms for the prevention, diagnosis, and treatment of T2D.
Shiga toxin-converting bacteriophages (Stx phages) carry the stx gene and convert nonpathogenic bacterial strains into Shiga toxin-producing bacteria. There is limited understanding of the effect that an Escherichia coli (E. coli) clustered regularly interspaced short palindromic repeats (CRISPR)-Cas adaptive immune system has on Stx phage lysogen. We investigated heat-stable nucleoid-structuring (H-NS) mutation-mediated CRISPR-Cas activation and its effect on E. coli Stx2 phage lysogen. The Δhns mutant (MG1655Δhns) of the E. coli K-12 strain MG1655 was obtained. The Δhns mutant lysogen that was generated after Stx phage lysogenic infection had a repressed growth status and showed subdued group behavior, including biofilm formation and swarming motility, in comparison to the wild-type strain. The de-repression effect of the H-NS mutation on CRISPR-Cas activity was then verified. The results showed that cas gene expression was upregulated and the transformation efficiency of the wild-type CRISPR plasmids was decreased, which may indicate activation of the CRISPR-Cas system. Furthermore, the function of CRISPR-Cas on Stx2 phage lysogen was investigated by activating the CRISPR-Cas system, which contains an insertion of the protospacer regions of the Stx2 phage Min27. The phage release and toxin production of four lysogens harboring the engineered CRISPRs were investigated. Notably, in the supernatant of the Δhns mutant lysogen harboring the Min27 spacer, both the progeny phage release and the toxin production were inhibited after mitomycin C induction. These observations demonstrate that the H-NS mutation-activated CRISPR-Cas system plays a role in modifying the effects of the Stx2 phage lysogen. Our findings indicated that H-NS mutation-mediated CRISPR-Cas activation in E. coli protects bacteria against Stx2 phage lysogeny by inhibiting the phage release and toxin production of the lysogen.
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