N6-methyladenosine (m6A) in pancreatic cancer: Regulatory mechanisms and future direction.

N6-methyladenosine (m6A), the most abundant RNA modification in eukaryotes, plays a pivotal role in regulating many cellular and biological processes. Aberrant m6A modification has recently been involved in carcinogenesis in various cancers, including pancreatic cancer. Pancreatic cancer is one of the deadliest cancers. It is a heterogeneous malignant disease characterized by a plethora of diverse genetic and epigenetic events. Increasing evidence suggests that dysregulation of m6A regulatory factors, such as methyltransferases, demethylases, and m6A-binding proteins, profoundly affects the development and progression of pancreatic cancer. In addition, m6A regulators and m6A target transcripts may be promising early diagnostic and prognostic cancer biomarkers, as well as therapeutic targets. In this review, we highlight the biological functions and mechanisms of m6A in pancreatic cancer and discuss the potential of m6A modification in clinical applications.

Effect of quorum-sensing molecule 2-phenylethanol and ARO genes on Saccharomyces cerevisiae biofilm.

Biofilms are a form of microbial community that can be beneficial for industrial fermentation because of their remarkable environmental resistance. However, the mechanism of biofilm formation in Saccharomyces cerevisiae remains to be fully explored, and this may enable improved industrial applications for this organism. Although quorum-sensing (QS) molecules are known to be involved in bacteria biofilm formation, few studies have been undertaken with these in fungi. 2-phenylethanol (2-PE) is considered a QS molecule in S. cerevisiae. Here, we found that exogenous 2-PE could stimulate biofilm formation at low cell concentrations. ARO8p and ARO9p are responsible for the synthesis of 2-PE and were crucial to the formation of biofilm. Deletion of the ARO8 and ARO9 genes reduced the content of 2-PE in the early stage of fermentation, reduced ethanol yield and decreased biofilm formation. The expression of FLOp, which is involved in cell adhesion, and the content of extracellular polysaccharides of mutant strains ΔARO8 and ΔARO9 were also significantly reduced. These findings indicate that the production of 2-PE had a positive effect on biofilm formation in S. cerevisiae, thereby providing further key details for studying the formation of biofilm mechanism in the future. KEY POINTS: • Quorum-sensing molecule 2-PE positively affects biofilm formation in S. cerevisiae. • 2-PE synthetic genes ARO8 and ARO9 deletion reduced extracellular polysaccharide. • ARO8 and ARO9 deletion reduced the gene expression of the FLO family.

Transplantation of cryopreserved human umbilical cord blood-derived endothelial progenitor cells induces recovery of carotid artery injury in nude rats.

INTRODUCTION: Transplantation of endothelial progenitor cells (EPCs) restores endothelial function in patients with endothelial dysfunction and initial denudation. The goal of the present study was to determine the effect of cryopreserved human umbilical cord blood (UCB)-derived EPC infusion on the repair of carotid artery injury in nude rats. METHODS: Mononuclear cells (MNCs) from human cryopreserved UCB and peripheral blood (PB) of patients with cardiovascular diseases and healthy volunteers were cultured in a conditioned medium. The in vitro migration, proliferation, adhesion, and survival capacities, as well as paracrine cytokine release of EPCs were investigated. EPC homing, induced reendothelialization, and the effect on neointima formation were also assessed in vivo. RESULTS: Patient-derived PB EPCs (PPB-EPCs) displayed decreased migration, proliferation, adhesion, and survival capabilities as compared to PB-EPCs from healthy volunteers (HPB-EPCs) and cryopreserved UCB-EPCs. However, there was no difference in the release of vascular endothelial growth factor (VEGF) and stromal cell derived factor 1 (SDF-1) between the three groups. Two weeks after transplantation, more labeled UCB-EPCs and HPB-EPCs than PPB-EPCs were found by cell tracking in the injury zone. Administration of PPB-EPCs, HPB-EPCs, and UCB-EPCs enhanced reendothelialization and inhibited neointima formation compared to the saline control. However, UCB-EPC and HPB-EPC infusion showed a greater improvement than PPB-EPCs. CONCLUSIONS: Cryopreserved UCB-MNCs derived EPCs and HPB-EPCs show better responses to cytokines and vascular injury than PPB-EPCs. Thus, cryopreservation and delivery of cryopreserved autogenous UCB-EPCs or HPB-EPCs may be a promising vasculoprotective approach for patients with multiple cardiovascular risk factors.

Regulation of Cellular Response Pattern to Phosphorus Ion is a New Target for the Design of Tissue-Engineered Blood Vessel.

Regulation of cellular response pattern to phosphorus ion (PI) is a new target for the design of tissue-engineered materials. Changing cellular response pattern to high PI can maintain monocyte/macrophage survival in TEBV and the signal of increasing PI can be converted by klotho to the adenosine signals through the regulation of energy metabolism in monocytes/macrophages.

[Effects of Klotho protein on proliferation, migration, adhesion and vascular endothelial growth factor expression of human umbilical vein cells].

OBJECTIVE: To explore the effects of anti-aging Klotho protein in the proliferation, migration and adhesiveness of human umbilical vein endothelial cell (HUVEC) and its influence of vascular endothelial growth factor (VEGF) expression in HUVEC. METHODS: HUVEC were treated for 24 h with various concentrations of Klotho protein (final concentrations of 0.1, 1, 10 nmol/L respectively). At the same time, HUVEC treated with PBS, 10 nmol/L VEGF and 10 nmol/L Klotho protein plus AKT inhibitors served as blank control, positive control and AKT signaling pathway inhibition group respectively. The effects of Klotho proteins on proliferation, migration and adhesiveness of HUVEC were determined by thiazolyl blue tetrazolium bromide (MTT), scratches, Transwell and cell adhesion assays respectively. After HUVEC exposed to Klotho protein, the induced function of VEGF expression was measured by Western blot analysis. RESULTS: The MTT results showed that the A values of 0.1, 1, 10 nmol/L Klotho protein group increased respectively to 0.63 ± 0.03, 0.71 ± 0.04, 0.80 ± 0.04, control to the blank group (0.59 ± 0.03, F = 9.32, all P < 0.05). The scratches tests showed that compared with the blank control (9.40 ± 2.07)%, the cell migration rates of 0.1, 1, 10 nmol/L Klotho protein group increased significantly to (12.28 ± 0.62)%, (31.66 ± 1.50)%,(36.69 ± 0.79)%, (F = 9.50, all P < 0.05). Transwell assay found that cell migration count of 0.1, 1, 10 nmol/L Klotho protein group increased to 95.88 ± 9.54, 143.13 ± 7.83, 178 ± 12.77, higher than the blank control group (80.13 ± 12.19), the difference was statistically significant (F = 11.51, all P < 0.05). In cell adhesion assays, the number of cell adhesion increased to 59.60 ± 5.13, 78.40 ± 7.16, 114.60 ± 5.55 at 0.1, 1, 10 nmol/L Klotho protein group versus the blank control (49.40 ± 6.23) and the difference was also statistically significant (F = 9.75, all P < 0.05). Using Western blot, the expressions of VEGF were significantly induced to 0.46 ± 0.02,0.71 ± 0.12,0.81 ± 0.16 at 0.1, 1, 10 nmol/L Klotho protein group versus blank control group (0.35 ± 0.08, F = 8.95, all P < 0.05). CONCLUSION: Klotho protein can promote the proliferation, migration and adhesiveness of HUVEC and induce a significant expression of VEGF, and its functions are related with the AKT signaling pathway.

Safety and efficacy of degradable vs. permanent polymer drug-eluting stents: a meta-analysis of 18,395 patients from randomized trials.

BACKGROUND: Degradable polymer drug-eluting stents (DP-DES) represent a promising strategy to improve the delayed healing and hypersensitive reaction in the vessel. However, the efficacy and safety of DP-DES vs. permanent polymer drug-eluting stents (PP-DES) are less well defined. The aim of this meta-analysis was to compare the total, short (<30 days), mid (30 days-1 year) and long (>1 year) term outcomes of DP-DES vs. PP-DES METHODS: PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for randomized clinical trials to compare any of approved DP- and PP-DES. Efficacy endpoints were target-lesion revascularization (TLR) and in-stent late loss (ISLL). Safety endpoints were death, myocardial infarction (MI), and composite of definite and probable stent thrombosis (ST). RESULTS: The meta-analysis included 19 RCTs (n=18,395) with interesting results. As compared with DES, there was a significantly reduced very late ST (OR [95% CI]=0.42 [0.24-0.77], p=0.852) and ISLL (OR [95% CI]=-0.07 [-0.12-0.02], p=0.000) in DP-DES patients. However, there were no differences between DP-DES and PP-DES for other safety and efficiency outcomes, except that the stratified analysis showed a significant decreased TLR with DP-DES as compared to paclitaxel-eluting stent (OR [95% CI]=0.41 [0.20-0.81], p=0.457). CONCLUSIONS: DP-DES are more effective in reducing very late ST and ISLL, as well as comparable to PP-DES with regard to death, TLR and MI. Further large RCTs with long-term follow-up are warranted to better define the relative merits of DP-DES.