Search

Background: N6-methyladenosine (m6A) modification is involved in tumorigenesis and progression as well as closely correlated with stem cell differentiation and pluripotency. Moreover, tumor progression includes the acquisition of stemness characteristics and accumulating loss of differentiation phenotype. Therefore, we integrated m6A modification and stemness indicator mRNAsi to classify patients and predict prognosis for LGG. Methods: We performed consensus clustering, weighted gene co-expression network analysis, and least absolute shrinkage and selection operator Cox regression analysis to identify an m6A regulation- and mRNAsi-related prognostic index (MRMRPI). Based on this prognostic index, we also explored the differences in immune microenvironments between high- and low-risk populations. Next, immunotherapy responses were also predicted. Moreover, single-cell RNA sequencing data was further used to verify the expression of these genes in MRMRPI. At last, the tumor-promoting and tumor-associated macrophage polarization roles of TIMP1 in LGG were validated by in vitro experiments. Results: Ten genes (DGCR10, CYP2E1, CSMD3, HOXB3, CABP4, AVIL, PTCRA, TIMP1, CLEC18A, and SAMD9) were identified to construct the MRMRPI, which was able to successfully classify patients into high- and low-risk group. Significant differences in prognosis, immune microenvironment, and immunotherapy responses were found between distinct groups. A nomogram integrating the MRMRPI and other prognostic factors were also developed to accurately predict prognosis. Moreover, in vitro experiments illustrated that inhibition of TIMP1 could inhibit the proliferation, migration, and invasion of LGG cells and also inhibit the polarization of tumor-associated macrophages. Conclusion: These findings provide novel insights into understanding the interactions of m6A methylation regulation and tumor stemness on LGG development and contribute to guiding more precise immunotherapy strategies. [ABSTRACT FROM AUTHOR]

Association between CD69 and EGR1 levels and coronary heart disease (CHD) patients without reflow after percutaneous coronary intervention (PCI) was investigated. Data of 156 patients undergoing PCI from September 2014 to December 2016 in People's Hospital of Hunan Province were analyzed, and they were divided into 72 cases in reflow group (group A) and 84 cases in no-reflow group (group B) according to the patient's postoperative blood flow. Another 70 volunteers undergoing normal physical examination in the same period were selected as control group (group C). The venous blood was extracted from patients before operation, at 5 min, 2 h and 6 months after operation, the serum CD69 and EGR1 levels were detected with flow cytometry and RT-qPCR methods, and association between CD69 and EGR1 levels and postoperative blood flow recovery was analyzed. CD69 expression before and 2 h after operation in group A was significant (P<0.05), and a difference in patients at 6 months after operation between group A, B and group C (P<0.05). The CD69 expression in group A was significantly lower than that in group B (P<0.05), but in group B was significantly higher than that in group C (P<0.05). The EGR1 expression in group A was significantly higher than that in group B (P<0.05), but in group B was significantly lower than that in group C (P<0.05). Multivariate logistic regression analysis revealed that CD69 (OR=6.424, P=0.025) and EGR1 (OR=3.684, P=0.013) were independent risk factors for patients without reflow after undergoing PCI. After undergoing PCI in CHD patients, if there was an increase in CD69 level and a significant decrease in EGR1 level in the early postoperative period, the patient may be suspected of having no-reflow and checked in time to improve the patient's therapeutic effect. [ABSTRACT FROM AUTHOR]

Expression and clinical significance of CD69 and early growth response (EGR1) in plasma of patients with coronary heart disease (CHD) were investigated. A total of 194 patients with CHD and 130 healthy subjects, respectively, were selected as CHD and control group, clinical data were collected and coronary angiography was performed. RT-qPCR was used to detect the expression of EGR1. Flow cytometry was used to detect the expression level of CD69 and the receiver operating characteristic curve was used to analyze the values of relative expression of CD69 and EGR1. The relative expression of CD69 in plasma of patients with CHD was higher than that in control group, while the relative expression of EGR1 was lower than that in control group. The relative expression of EGR1 in plasma of patients with CHD was negatively correlated with lipoprotein a [Lp(a)] and high sensitive C-reactive protein (hs-CRP) (r=−0.394 and −0.524, P<0.05), and the relative expression of CD69 in peripheral blood was positively correlated with [Lp(a)] and hs-CRP (r=0.352 and 0.402, P<0.05). The area under curve (AUC) of the relative expression of CD69 in peripheral blood of patients with CHD in evaluating the course of the disease of patients was 0.889 (95% CI: 0.822–0.958). The AUC of the relative expression of EGR1 in plasma in evaluating the course of the disease of patients was 0.933 (95% CI: 0.867–0.978). By the combined detection of CD69 and EGR1, it was found that the AUC was 0.954 (95% CI: 0.887–0.982). The expression level of EGR1 in plasma of patients with CHD decreased, while the expression level of CD69 increased, and both of them were related to the severity of the disease of patients, which could be used as an indicator to evaluate the progression of the patients' conditions. [ABSTRACT FROM AUTHOR]

The level of CHB virus (HBV) core antibody (HBcAb) is different in four stages of chronic HBV infection and may be used for differential diagnosis of the natural history of chronic HBV infection. To address this question, we examined multiple blood biomarkers and assessed the efficacy to diagnose different stages of chronic HBV infection. The quantitative detection of HBcAb, hepatitis B surface antigen (HBsAg), HBV DNA, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and platelet count (PLT) were determined in the serum of 73 cases of low-replicative phase (LR), 46 cases of immune-tolerant phase (IT), 44 cases of immune clearance phase (IC), and 57 cases of HBeAg-negative hepatitis (ENH). Differentiating performance of these serum protein levels was analyzed by receiver operating characteristic (ROC) curve analysis. Our results showed that the levels of HBcAb, ALT, and AST levels were significantly higher in IC and ENH than those in LR and IT (both P ≤ 0.001). The levels of HBV DNA and HBsAg were higher in IC and IT than those in LR and ENH (both P ≤ 0.001). Logistic regression models showed that HBcAb, HBsAg, HBV DNA, ALT, and AST were the independent variables, respectively, and when combined, they provided high diagnostic accuracy for the staging of CHB. To sum up, HBcAb quantification is a new index, which can reflect whether the liver is in the immune activation state of HBV infection, and is related to the inflammatory state of the host liver. The combined detection of HBcAb quantification and other indicators has showed promising efficiency for staging of IC and ENH and can assist the diagnosis and treatment of CHB. [ABSTRACT FROM AUTHOR]

A novel mushroom-like electrochemical immunoassay for the ultrasensitive detection of histone acetyltransferase activity (HAT p300) has been established on account of the new composite graphene oxide (GO) nanolayer. The immunoassay involves immobilization of substrate peptide onto Au electrode, acetylation in lysine of substrate peptide, and the interaction between acetyl group of lysine and acetyl-antibody (Ab Ac) of the GO nanolayer. The GO nanolayer comprises large amounts of methylene blue molecules (MB), giving rise to large signal amplification. Only in the presence of HAT p300, an obvious electrochemical signal appears and the peak linear current is proportion to the HAT p300 concentrations ranging from 0.01 to 150 nM with a detection limit of 0.0036 nM. The great enhancement on sensitivity of the proposed mushroom-like immunosensor derives from both the constructed Faraday cage and the extended outer Helmholtz plane (OHP). Further, the immunosensor with excellent sensitivity and selectivity can be applied for the HAT p300 activity detection in Hela cell lysates, serum and urine, hinting an improved and splendid analytical performance. Briefly, this stable, simple and ultrasensitive electrochemical immunoassay has considerable promise for further applications in the HATs-interrelated epigenetic studies and drug development. A novel mushroom-like electrochemical immunosensor for the ultrasensitive detection of histone acetyltransferase activity (HAT p300) has been reported, which shows promise for further applications in the HATs-targeted epigenetic research and drug discovery. Image 1 • An ultrasensitive mushroom-like electrochemical immunosensor is developed. • The proposed strategy can be applied for probing the HAT p300 activity. • The detection sensitivity of the novel method is improved sharply. • Mechanism is the constructed Faraday cage and extended outer Helmholtz plane. • The HAT-based immunosensor is also adopted for the screening of inhibitor. [ABSTRACT FROM AUTHOR]

Herein, we reported a unique G4-nanowires-mediated switch-modulated electrochemical biosensing platform for sensitive nickel ion (Ni2+) and histidine (His) detection. The as-proposed electrochemical strategy got the utmost out of the peculiar characteristics including addressable and highly stable DNA-tetrahedron substrate; Terminal deoxynucleotidyl transferase (TdT)-generated stochastic G4-nanowires with unique peroxidase-mimic DNAzyme activity; freewheeling and interesting electrochemical switch modulated by Ni2+ and His. As expected, the direct effect of Ni2+ on the peroxidase-mimic DNAzyme activity of the G4-nanowires could be associated with the inhibition and decrease of the signal significantly. Moreover, the emerging His gave rise to a resurgence of electrochemical signal owing to the affinity between Ni2+ and His. In view of these, the proposed biosensor displayed a suitable detection limit of 0.15 nM for Ni2+ or 1.2 nM for His, respectively (S/N = 3). More importantly, taking on Ni2+ and His as the model inputs, representative NOT, YES and IMPLICATION logic gates had been accomplished and outputted by readable electrochemical signal change. It is expected to that the unique G4-nanowires-based electrochemical assay hold huge potentials in applications including environmental monitoring, pharmaceutical analysis and clinical diagnosis. A novel unique G4-nanowires-mediated switch-modulated electrochemical biosensor with excellent sensitivity and selectivity for Ni2+ and His detection was established and this electrochemical logic system may pave the way for developing complicated DNA-based Boolean computing. Unlabelled Image • Unique G4-nanowires are synthesized by TdT-derived polymerization. • The mechanism is the peroxidase-mimic DNAzyme activity of G4-nanowires. • The proposed strategy can be applied for probing nickel ion and histidine. • The biosensor can be adopted for complicated DNA-based Boolean computing. [ABSTRACT FROM AUTHOR]