Identification of cytokines involved in hepatic differentiation of mBM-MSCs under liver-injury conditions

AIM: To identify the key cytokines involved in hepatic differentiation of mouse bone marrow mesenchymal stem cells (mBM-MSCs) under liver-injury conditions. METHODS: Abdominal injection of CCl4 was adopted to duplicate a mouse acute liver injury model. Global gene expression analysis was performed to evaluate the potential genes involved in hepatic commitment under liver-injury conditions. The cytokines involved in hepatic differentiation of mBM-MSCs was function-ally examined by depletion experiment using specifi c antibodies, followed by rescue experiment and direct inducing assay. The hepatic differentiation was characterized by the expression of hepatic lineage genes and proteins, as well as functional features. RESULTS: Cytokines potentially participating in hepatic fate commitment under liver-injury conditions were initially measured by microarray. Among the up-regulated genes determined, 18 cytokines known to closely relate to liver growth, repair and development, were selected for further identif ication. The f ibroblast growth factor-4 (FGF-4), hepatocyte growth factor (HGF) and oncostatin M (OSM) were fi nally found to be involved in hepatic differentiation of mBM-MSCs under liver-injury conditions. Hepatic differentiation could be dramatically decreased after removing FGF-4, HGF and OSM from the liver-injury conditioned medium, and could be rescued by supplementing these cytokines. The FGF-4, HGF and OSM play different roles in the hepatic differentiation of mBM-MSCs, in which FGF-4 and HGF are essential for the initiation of hepatic differentiation, while OSM is critical for the maturation of hepatocytes. CONCLUSION: FGF-4, HGF and OSM are the key cytokines involved in the liver-injury conditioned medium for the hepatic differentiation of mBM-MSCs.

Epoxyeicosatrienoic acids are related to early neurological deterioration and mediated by EPHX2 gene variants in acute minor ischemic stroke

Objective To investigate the association of plasma epoxyeicosatrienoic acids(EETs)with early neurological deterioration(END),and whether EETs are mediated by EPHX2 gene variants in patients with minor ischemic stroke(MIS).Methods This is a prospective,multicenter observational study in patients with acute MIS in the Chinese population.Acute MIS patients with the first onset and onset within 24 hours who were admitted to Deyang People's Hospital.

Analysis of clinical significance on the special thromboelastograph graphics

Objective Through the analysis of the special thromboelastography (TEG) graphics to improve the ability of analysis and identification the TEG and provide more valuable results for clinical practice.Methods This study is a retrospective study.Retrospective analysis

Study of FN1 and ZNF438 gene expression negatively regulated by androgen receptor in androgen-independent LNCaP cells

Objective To verify whether FN1 and ZNF438 are the androgen receptor(AR)target genes in LNCa P-AI cells and investigate the effects of AR on FN1 and ZNF438 gene expression.Methods Ch IP-PCR and agar-

Differential proteomics analysis of pathogenic unit of stasis-heat for acute intracerebral hemorrhage

Objective To clarify the biomarkers and molecular disorder mechanism of pathogenic unit of stasis-heat of acute intracerebral hemorrhage.Methods A total of 271 acute cerebral hemorrhage patients and their plasma samples were collected and classified into stasis-heat type and non-stasis-heat type according to Quantitative Diagnostic Scale of Stasis-heat Syndrome.Then 4 of each group were selected by 1∶1 paired design,and plasma samples of 4 pairs were collected or detecting differential proteins by tandem mass tag(TMT).The proteins expressed more than 1.3 times and P≤0.05 between the two groups were taken as differential proteins.The Ingenuity Pathway Analysis(IPA)bioinformatics software was performed in analyzing canonical pathways,upstream regulatory factor,molecular cellular functions,and protein interaction network of differential proteins.Results A total of 490 proteins were identified and quantified in each patient,of which 9 proteins were differentially expressed between the two groups(A1BG,ACTN1,CA1,CD44,CP,PRDX2,VCL,IgG H chain,and IGHV3-7),and A1BG,ACTN1,CA1,CD44,CP,PRDX2,and VCL were identified by IPA software.Compared with non-stasis-heat group,CD44 was down-regulated and the remaining six proteins were up-regulated.These proteins involved 5 canonical signaling pathways,2 upstream regulators and 5 kinds of molecules and cell functions.One associated functional network was generated with acceptable confidence.Conclusion Differential proteins reflecting the potential biomarkers of pathogenic unit of stasis-heat of the acute cerebral hemorrhage,are involved in the regulation of PI3K complexes,Akt and ERK-related cellular signaling pathways,which are closely related to inflammatory factors or their regulated upstream pathways.

Diplacone reduces homocysteine-induced vascular endothelial cell injury by inhibiting oxidative stress and NF-κB signaling pathway

Objective In this experiment,human umbilical vein endothelial cells were induced by HHcy in vitro,and the inflammatory damage model of vascular endothelial cells was established,the effect of Diplacone on human umbilical vein endothelial cells was observed by pretreatment with Diplacone,and further explored the possible protective mechanism of Diplacone on vascular endothelial cells.