Methyl-CpG binding protein 2 (MeCP2) has recently been characterized as an oncogene frequently amplified in several types of cancer. However, its precise role in gastric cancer (GC) and the molecular mechanism of MeCP2 regulation are still largely unknown. Here we report that MeCP2 is highly expressed in primary GC tissues and the expression level is correlated with the clinicopathologic features of GC. In our experiments, knockdown of MeCP2 inhibited tumor growth. Molecular mechanism of MeCP2 regulation was investigated using an integrated approach with combination of microarray analysis and chromatin immunoprecipitation sequencing (ChIP-Seq). The results suggest that MeCP2 binds to the methylated CpG islands of FOXF1 and MYOD1 promoters and inhibits their expression at the transcription level. Furthermore, we show that MeCP2 promotes GC cell proliferation via FOXF1-mediated Wnt5a/β-Catenin signaling pathway and suppresses apoptosis through MYOD1-mediated Caspase-3 signaling pathway. Due to its high expression level in GC and its critical function in driving GC progression, MeCP2 represents a promising therapeutic target for GC treatment.

In human hepatocellular carcinoma (HCC), aberrant expression of miRNAs correlates with tumor cell proliferation, apoptosis, invasion, and migration by targeting downstream proteins. miR-15b levels are reported increased in HCC tissues; however, they negatively correlate to HCC recurrence. Our aim was to understand the reason for this phenomenon. We used the reverse transcription-polymerase chain reaction (RT-PCR) to measure miR-15b-5p expression in both HCC tissues and HCC cell lines. Our results were consistent with the report. Using bioinformatics and luciferase reporter assays, we identified Rab1A as a novel and direct target of miR-15b-5p. Inhibiting the function of Rab1A with shRab1A also inhibited the growth of HCC cells and induced endoplasmic reticulum stress (ERS) and apoptosis. Similarly, suppressing Rab1A by overexpression of miR-15b-5p also inhibited cell growth and induced ERS and apoptosis. Moreover, re-expression of Rab1A rescued the miR-15b-5p -induced ERS, apoptosis, and growth inhibition in HCC cells. In vivo assays were further performed to testify them. Taken together, our data suggest that miR-15b-5p induces ERS, apoptosis, and growth inhibition by targeting and suppressing Rab1A, acting as a tumor suppressor gene in HCC. This finding suggests a novel relation among Rabs, miRNAs, and apoptosis.

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The approval of CD19 chimeric antigen receptor (CAR)-engineered T (CAR-T) cell products in B-cell malignancies represents a breakthrough in CAR-T cell immunotherapy. However, the remaining limitations concerning the graft-versus-host disease (GVHD) and other adverse effects (e.g., cytokine release syndromes [CRS] and neurotoxicity) still restrict their wider applications. Natural killer (NK) cells have been identified as promising candidates for CAR-based cellular immunotherapy because of their unique characteristics. No HLA-matching restriction and abundant sources make CAR-engineered NK (CAR-NK) cells potentially available to be off-the-shelf products that could be readily available for immediate clinical use. Therefore, researchers have gradually shifted their focus from CAR-T cells to CAR-NK cells in hematological malignancies. This review discusses the current status and applications of CAR-NK cells in hematological malignancies, as well as the unique advantages of CAR-NK cells compared with CAR-T cells. It also discusses challenges and prospects regarding clinical applications of CAR-NK cells.

Summary Mesenchymal stem cells (MSCs) are potential sources of cells for tissue repairing. However, little information is available regarding the therapeutic potency of intravenously transplanted MSCs for myocardial ischemia (MI). In the present study, MSCs were isolated from bone marrow of male rats and expanded in vitro. Three hours after ligation of left anterior descending artery, the transplanted group received an infusion of MSCs through the tail vein. At the same time, a coronary‐ligated control group was injected with culture medium. Homing of MSCs to the heart was assessed by expression of the Y chromosome sry gene using fluorescent in situ hybridization (FISH). At 1 week or 8 weeks after transplantation, sry positive cells were present in cardiac tissue in the transplanted group, but not in the hearts of control group. Cardiomyocytes, smooth muscle cells, and endothelial cells that bore sry gene were identified in transplanted group at 8 weeks after transplantation. Ultrastructural observation revealed that a large number of capillary and some immature myocytes were found to survive in the ischemia region. MSCs transplantation also decreased LVEDP pressure and −dP/dt, but increased LVSP and +dP/dt. The cardiac infarct size was significantly smaller in transplanted group than in control group. Our data suggest that intravenously transplanted MSCs improve cardiac performance and promote the regeneration of blood vessels and cardiomyocytes.

The relaxation process of the discharge channel near the anode in a long air gap was observed using a Schlieren system with a temporal resolution of 5 µs and a spatial resolution of 70 µm. The dynamic characteristics of the decay process in the vicinity of the anode are obtained. The discharge channel evolves just as a growing mushroom in nature during the relaxation phase. Two physical quantities, angle θ and velocity v, are defined to describe the process in this paper. The average value of the angle and velocity under lightning impulses are 71.7° and 3.3 m s −1 respectively, while 7.7 m s −1 under switching impulses. A simplified model was established to simulate the formation of mushroom-shaped channel. The simulation and experimental results show that the formation and development of the mushroom-shaped channel are due to two factors. One is the convection of the high temperature and high pressure air near the anode produced by the first corona discharge; the other is the ionic migration. These two factors result in the phenomena that the cooling process in the vicinity of the anode is much more efficient than further into the gap, whereas the thermal conductivity of the anode may have little contribution to that.

AIM:To investigate the signaling pathways implicated in phosphatidylethanolamine (PE)-induced apoptosis of human hepatoma HepG2 cells. METHODS:Inhibitory effects of PE on human h e p a t o m a H e p G 2 c e l l s w e r e d e t e c t e d b y 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell cycle, apoptosis and mitochondrial transmembrane potential (ΔΨm) were analyzed by flow cytometry. Immunocytochemical assay and Western blotting were used to examine Bcl-2, Bax and caspase-3 protein levels in HepG2 cells treated with PE. RESULTS:PE inhibited the growth of HepG2 cells in a dose-and time-dependent manner. It did not affect the cell cycle, but induced apoptosis. PE significantly decreased ΔΨm at 0.25, 0.5 and 1 mmol/L, respectively, suggesting that PE induces cell apoptosis by decreasing the mitochondrial transmembrane potential. The Bcl-2 expression level induced by different concentrations of PE was lower than that in control groups. However, the Bax expression level induced by PE was higher than that in the control group. Meanwhile, PE increased the caspase-3 expression in a dose-and time-dependent manner. CONCLUSION:Exogenous PE induces apoptosis of human hepatoma HepG2 cells via the bcl-2/bax pathway.

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